山羊诱导性多能干细胞的研究
摘要
通过向体细胞中导入特定的转录因子可以将体细胞重编程为诱导性多能干细胞(induced pluripotent stem cells, iPSCs)。已经有很多物种成功地产生相应的iPSCs,但是在有蹄类家畜中,尤其是山羊,iPSCs建系成功的却很少。本研究主要目的是通过慢病毒携带人源的四个多能基因hOCT4,hSOX2,hKLF4和hcMYC-导入山羊体细胞,通过对诱导体系和培养体系的优化,成功将山羊体细胞重编程为iPSCs(giPSCs),在此基础上,使用同样的方法将克隆奶山羊体细胞重编程为iPSCs(tgiPSCs),并且将tgiPSCs作为供体细胞通过核移植技术,检测其能否在体外生产克隆胚胎。本文主要研究结果如下：
1.摸索出适合山羊iPSCs的诱导体系和培养体系
本试验在前人研究成果的基础上,首先使用干细胞无血清培养体系"KNOCKOUT-DMEM+KSR"分别添加人源白血病抑制因子(leukemia inhibitory factor,LIF),人源Beta-成纤维细胞生长因子(Beta-fibroblast growth factor,(3-FGF),以及两者都加。试验结果表明,培养体系中只添加LIF会导致giPSCs自动分化,而添加β-FGF或者两者都加可以维持giPSCs未分化的状态。
尝试家畜ESCs和iPSCs建系经常使用的培养基DMEM/F12和血清FBS,通过试验结果发现使用FBS对于山羊iPSCs未分化状态的维持要优于KSR。用形态学标准选择形态好的原代克隆进行扩增,有的克隆重编程效果不好,传至2-4代克隆会分化。能传代的克隆,在5代前基本都是用机械法进行传代。使用酶解法进行传代,有的克隆比较大,酶解后可以配合机械法,将大的克隆分成小的克隆,轻轻吹打成小的细胞团块,否则团块不容易吹开,形成大的细胞团,不利于克隆的形成。
2.重编程转基因克隆奶山羊体细胞产生iPSCs
实验室已经成功获得批量转基因克隆奶山羊,检测发现,转基因hLF已经很好地整合到这些克隆奶山羊体细胞的基因组中。在已取得成果的基础上,用转基因克隆奶山羊耳成纤维细胞作为体细胞,经过慢病毒感染进行重编程,成功获得带有hLF奶山羊iPSCs(tgiPSCs).通过检测发现,这些tgiPSCs表达干细胞多能基因OCT4,SOX2, cMYC,KLF4和NANOG;对AKP反应呈阳性；可以在体外形成类胚体,形成的类胚体含有三胚层组织；同时可以在裸鼠的体内形成畸胎瘤,通过HE染色发现,形成的畸胎瘤中也含有三胚层组织。
3.用tgiPSCs作为核移植供体细胞更有利于核移植胚胎的发育
使用转基因奶山羊皮肤成纤维细胞(tgFs)和转基因克隆奶山羊耳成纤维细胞诱导产生的iPSCs(tgiPSCs)作为供体细胞,通过核移植技术生产克隆胚胎,分别命名为：tgF-Embryos和tgiPSCs-Embryos,同时收集了山羊体内生产的胚胎,命名为：vivo-Embryos,三种胚胎都处于8-16细胞期。使用荧光定量PCR检测了IGFs家族基因在tgF-Embryos,tgiPSCs-Embryos和vivo-Embryos中的表达情况。结果表明,IGF-1, IGF-1R和IGF-2R三个基因在tgF-Embryos, tgiPSCs-Embryos和vivo-Embryos三种胚胎的8-16细胞阶段中的表达量没有显著性差异(p>0.05),但是IGF-2在tgiPSCs-Embryos中的表达量要比在tgF-Embryos中的表达量显著要低(p<0.01)。然而,IGF-2在tgiPSCs-Embryos和vivo-Embryos中的表达量没有显著性差异(p>0.05)。IGF-2在tgF-Embryos中的表达量要比在tgiPSCs-Embryos和vivo-Embryos中的表达量显著要高(p<0.01)。相对于在tgF-Embryos中的表达模式,IGFs家族基因(IGF-1,IGF-2, IGF-1R和IGF-2R)在tgiPSCs-Embryos的表达模式与在vivo-Embryos中的表达模式更接近。
Induced pluripotent stem cells(iPSCs) can be generated by reprogramming somatic cells with several combinations of genes encoding transcription factors(OCT3/4, SOX2, KLF4, cMYC, LIN28and NANOG). To date, iPSCs have been isolated from various species, but only limited information is available regarding goat iPSCs(giPSCs). The objectives of this study were that generate giPSCs from fetal goat primary ear fibroblasts using lentiviral transduction of four human(h) transcription factors:hOCT4, hSOX2, hKLF4and hcMYC. On the basis of the previous research, we generated tgiPSCs using the same method. Using tgiPSCs as donor cells which detected the ability of producing cloned embryos in vitro by nuclear transfer technique. The main findings are as follows:
1. Finding out the suitable induced system and culture system for giPSCs
Based on the results of previous studies, the experiment used serum-free culture system "KNOCKOUT-DMEM+KSR" which was added human sources LIF, human sources β-FGF, and both of them. The results indicated that the undifferentiated state of giPSCs could not be maintained in the culture system adding LIF. Then the undifferentiated state of giPSCs could be maintained in the culture system adding β-FGF or both β-FGF and LIF.
We tried to use DMEM/F12and FBS which were used in culturing livestock ESCs and iPSCs frequently. The result of experiment indicated that FBS is more suitable than KSR for culturing giPSCs. We selected primary clone for further expansion using the morphological criteria. Some clones would differentiate after2-4passages. Mechanical method were used to passage the good quality clone before5passages. Using enzymatic method, some clones is relatively large. After passaging with the enzymatic, the large clones should be devided into small clumps of cells using mechanical method. The large clump of cells was difficult to form a new clone.
2. Somatic cell of transgenic cloned dairy goats induced into giPSCs
Our laboratory had obtained a large batch of transgenic cloned dairy goats. The transgenic human lactoferrin(hLF) have already been integrated into the genome of them. Based on the achievement of the previous researchs, ear fibroblast cells of transgenic cloned dairy goats induced into transgenic giPSCs(tgiPSCs) harboring hLF using lentivirus. The result of experiment indicated that tgiPSCs expressed multiple pluripotent genes: OCT4, SOX2, cMYC, KLF4and NANOG; AKP reaction positive; formed embryoid body containing three mesodermal tissues in vitro; formed teratoma containing three germ layers.
3. TiPSCs as donor cell is more suitable to the development of nuclear transfer embryos
We use transgenic goat skin fibroblasts(tgFs) and tgiPSCs as donor cells to produce cloned embryos(tgF-Embryos and tgiPSC-Embryos), and also collected goat embryos producing in vivo. All of the three embryos are in the8-16cell stage. We compared the expression profile of growth-promoting genes(IGF-1and IGF-2) and their receptor genes(IGF-1R and IGF-2R) in tgF-Embryos, tgiPSC-Embryos, and vivo-Embryos by using RT-PCR. IGF-1regulates the growth-promoting activity of growth hormone through IGF-1receptors. The bioactivities of IGF-2are similar to those of IGF-1, and the expression of IGF-1and IGF-2significantly affect the reprogramming of the derived embryos and their subsequent development. At the8-16-cell stage, the expression of IGF-1, IGF-1R and IGF-2R was not significantly different among tgF-Embryos, tgiPSC-Embryos and vivo-Embryos, but the expression of IGF-2was significantly lower in tgiPSC-Embryos than in tgF-Embryos. However, there was no significant difference in the expression of IGF-2in tgiPSC-Embryos and vivo-Embryos. IGF-2expression in embryos generated using NT was relatively higher than that in vivo-Embryos. The expression profile of insulin-like growth factor(IGFs) family genes(IGF-1, IGF-2, IGF-1R and IGF-2R) in tgiPSC-Embryos is closer to vivo-Embryos than tgF-Embryos.
1.摸索出适合山羊iPSCs的诱导体系和培养体系
本试验在前人研究成果的基础上,首先使用干细胞无血清培养体系"KNOCKOUT-DMEM+KSR"分别添加人源白血病抑制因子(leukemia inhibitory factor,LIF),人源Beta-成纤维细胞生长因子(Beta-fibroblast growth factor,(3-FGF),以及两者都加。试验结果表明,培养体系中只添加LIF会导致giPSCs自动分化,而添加β-FGF或者两者都加可以维持giPSCs未分化的状态。
尝试家畜ESCs和iPSCs建系经常使用的培养基DMEM/F12和血清FBS,通过试验结果发现使用FBS对于山羊iPSCs未分化状态的维持要优于KSR。用形态学标准选择形态好的原代克隆进行扩增,有的克隆重编程效果不好,传至2-4代克隆会分化。能传代的克隆,在5代前基本都是用机械法进行传代。使用酶解法进行传代,有的克隆比较大,酶解后可以配合机械法,将大的克隆分成小的克隆,轻轻吹打成小的细胞团块,否则团块不容易吹开,形成大的细胞团,不利于克隆的形成。
2.重编程转基因克隆奶山羊体细胞产生iPSCs
实验室已经成功获得批量转基因克隆奶山羊,检测发现,转基因hLF已经很好地整合到这些克隆奶山羊体细胞的基因组中。在已取得成果的基础上,用转基因克隆奶山羊耳成纤维细胞作为体细胞,经过慢病毒感染进行重编程,成功获得带有hLF奶山羊iPSCs(tgiPSCs).通过检测发现,这些tgiPSCs表达干细胞多能基因OCT4,SOX2, cMYC,KLF4和NANOG;对AKP反应呈阳性；可以在体外形成类胚体,形成的类胚体含有三胚层组织；同时可以在裸鼠的体内形成畸胎瘤,通过HE染色发现,形成的畸胎瘤中也含有三胚层组织。
3.用tgiPSCs作为核移植供体细胞更有利于核移植胚胎的发育
使用转基因奶山羊皮肤成纤维细胞(tgFs)和转基因克隆奶山羊耳成纤维细胞诱导产生的iPSCs(tgiPSCs)作为供体细胞,通过核移植技术生产克隆胚胎,分别命名为：tgF-Embryos和tgiPSCs-Embryos,同时收集了山羊体内生产的胚胎,命名为：vivo-Embryos,三种胚胎都处于8-16细胞期。使用荧光定量PCR检测了IGFs家族基因在tgF-Embryos,tgiPSCs-Embryos和vivo-Embryos中的表达情况。结果表明,IGF-1, IGF-1R和IGF-2R三个基因在tgF-Embryos, tgiPSCs-Embryos和vivo-Embryos三种胚胎的8-16细胞阶段中的表达量没有显著性差异(p>0.05),但是IGF-2在tgiPSCs-Embryos中的表达量要比在tgF-Embryos中的表达量显著要低(p<0.01)。然而,IGF-2在tgiPSCs-Embryos和vivo-Embryos中的表达量没有显著性差异(p>0.05)。IGF-2在tgF-Embryos中的表达量要比在tgiPSCs-Embryos和vivo-Embryos中的表达量显著要高(p<0.01)。相对于在tgF-Embryos中的表达模式,IGFs家族基因(IGF-1,IGF-2, IGF-1R和IGF-2R)在tgiPSCs-Embryos的表达模式与在vivo-Embryos中的表达模式更接近。
Induced pluripotent stem cells(iPSCs) can be generated by reprogramming somatic cells with several combinations of genes encoding transcription factors(OCT3/4, SOX2, KLF4, cMYC, LIN28and NANOG). To date, iPSCs have been isolated from various species, but only limited information is available regarding goat iPSCs(giPSCs). The objectives of this study were that generate giPSCs from fetal goat primary ear fibroblasts using lentiviral transduction of four human(h) transcription factors:hOCT4, hSOX2, hKLF4and hcMYC. On the basis of the previous research, we generated tgiPSCs using the same method. Using tgiPSCs as donor cells which detected the ability of producing cloned embryos in vitro by nuclear transfer technique. The main findings are as follows:
1. Finding out the suitable induced system and culture system for giPSCs
Based on the results of previous studies, the experiment used serum-free culture system "KNOCKOUT-DMEM+KSR" which was added human sources LIF, human sources β-FGF, and both of them. The results indicated that the undifferentiated state of giPSCs could not be maintained in the culture system adding LIF. Then the undifferentiated state of giPSCs could be maintained in the culture system adding β-FGF or both β-FGF and LIF.
We tried to use DMEM/F12and FBS which were used in culturing livestock ESCs and iPSCs frequently. The result of experiment indicated that FBS is more suitable than KSR for culturing giPSCs. We selected primary clone for further expansion using the morphological criteria. Some clones would differentiate after2-4passages. Mechanical method were used to passage the good quality clone before5passages. Using enzymatic method, some clones is relatively large. After passaging with the enzymatic, the large clones should be devided into small clumps of cells using mechanical method. The large clump of cells was difficult to form a new clone.
2. Somatic cell of transgenic cloned dairy goats induced into giPSCs
Our laboratory had obtained a large batch of transgenic cloned dairy goats. The transgenic human lactoferrin(hLF) have already been integrated into the genome of them. Based on the achievement of the previous researchs, ear fibroblast cells of transgenic cloned dairy goats induced into transgenic giPSCs(tgiPSCs) harboring hLF using lentivirus. The result of experiment indicated that tgiPSCs expressed multiple pluripotent genes: OCT4, SOX2, cMYC, KLF4and NANOG; AKP reaction positive; formed embryoid body containing three mesodermal tissues in vitro; formed teratoma containing three germ layers.
3. TiPSCs as donor cell is more suitable to the development of nuclear transfer embryos
We use transgenic goat skin fibroblasts(tgFs) and tgiPSCs as donor cells to produce cloned embryos(tgF-Embryos and tgiPSC-Embryos), and also collected goat embryos producing in vivo. All of the three embryos are in the8-16cell stage. We compared the expression profile of growth-promoting genes(IGF-1and IGF-2) and their receptor genes(IGF-1R and IGF-2R) in tgF-Embryos, tgiPSC-Embryos, and vivo-Embryos by using RT-PCR. IGF-1regulates the growth-promoting activity of growth hormone through IGF-1receptors. The bioactivities of IGF-2are similar to those of IGF-1, and the expression of IGF-1and IGF-2significantly affect the reprogramming of the derived embryos and their subsequent development. At the8-16-cell stage, the expression of IGF-1, IGF-1R and IGF-2R was not significantly different among tgF-Embryos, tgiPSC-Embryos and vivo-Embryos, but the expression of IGF-2was significantly lower in tgiPSC-Embryos than in tgF-Embryos. However, there was no significant difference in the expression of IGF-2in tgiPSC-Embryos and vivo-Embryos. IGF-2expression in embryos generated using NT was relatively higher than that in vivo-Embryos. The expression profile of insulin-like growth factor(IGFs) family genes(IGF-1, IGF-2, IGF-1R and IGF-2R) in tgiPSC-Embryos is closer to vivo-Embryos than tgF-Embryos.
引文
[1]Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell,2006,126:663-676.
[2]Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell,2007,131:861-872.
[3]Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie J, Jonsdottir GA, Ruotti V, Stewart R, Slukvin Ⅱ, Thomson JA. Induced pluripotent stem cell lines derived from human somatic cells. Science,2007,318:1917-1920.
[4]Ren J, Pak Y, He L, Qian L, Gu Y, Li H, Rao L, Liao J, Cui C, Xu X, Zhou J, Ri H, Xiao L. Generation of hircine-induced pluripotent stem cells by somatic cell reprogramming. Cell Res,2011, 21:849-853.
[5]Bao L, He L, Chen J, Wu Z, Liao J, Rao L, Ren J, Li H, Zhu H, Qian L, Gu Y, Dai H, Xu X, Zhou J, Wang W, Cui C, Xiao L. Reprogramming of ovine adult fibroblasts to pluripotency via drug-inducible expression of defined factors. Cell Res,2011,21:600-608.
[6]Li Y, Cang M, Lee AS, Zhang K, Liu D. Reprogramming of sheep fibroblasts into pluripotency under a drug-inducible expression of mouse-derived defined factors. PLoS One,2011,6:e15947.
[7]Liu J, Balehosur D, Murray B, Kelly JM, Sumer H, Verma PJ. Generation and characterization of reprogrammed sheep induced pluripotent stem cells. Theriogenology,2012,77:338-346 e331.
[8]Deng Y, Liu Q, Luo C, Chen S, Li X, Wang C, Liu Z, Lei X, Zhang H, Sun H, Lu F, Jiang J, Shi D. Generation of induced pluripotent stem cells from buffalo (Bubalus bubalis) fetal fibroblasts with buffalo defined factors. Stem Cells Dev,2012,21:2485-2494.
[9]Han X, Han J, Ding F, Cao S, Lim SS, Dai Y, Zhang R, Zhang Y, Lim B, Li N. Generation of induced pluripotent stem cells from bovine embryonic fibroblast cells. Cell Res,2011,21:1509-1512.
[10]Huang B, Li T, Alonso-Gonzalez L, Gorre R, Keatley S, Green A, Turner P, Kallingappa PK, Verma V, Oback B. A virus-free poly-promoter vector induces pluripotency in quiescent bovine cells under chemically defined conditions of dual kinase inhibition. PLoS One,2011,6:e24501.
[11]Esteban MA, Xu J, Yang J, Peng M, Qin D, Li W, Jiang Z, Chen J, Deng K, Zhong M, Cai J, Lai L, Pei D. Generation of induced pluripotent stem cell lines from Tibetan miniature pig. J Biol Chem, 2009,284:17634-17640.
[12]Ezashi T,Telugu BP,Alexenko AP, Sachdev S, Sinha S, Roberts RM. Derivation of induced pluripotent stem cells from pig somatic cells. Proc Natl Acad Sci USA,2009,106:10993-10998.
[13]Fan N, Chen J, Shang Z, Dou H, Ji G, Zou Q, Wu L, He L, Wang F, Liu K, Liu N, Han J, Zhou Q,Pan D,Yang D,Zhao B,Ouyang Z,Liu Z,Zhao Y,Lin L, Zhong C,Wang Q,Wang S,Xu Y, Luan J, Liang Y, Yang Z, Li J, Lu C, Vajta G, Li Z, Ouyang H, Wang H, Wang Y, Yang Y,Liu Z, Wei H, Luan Z, Esteban MA, Deng H, Yang H, Pei D, Li N, Pei G, Liu L, Du Y, Xiao L, Lai L. Piglets cloned from induced pluripotent stem cells. Cell Res,2013,23:162-166.
[14]Wu Z, Chen J, Ren J, Bao L, Liao J, Cui C, Rao L, Li H, Gu Y, Dai H, Zhu H, Teng X, Cheng L, Xiao L. Generation of pig induced pluripotent stem cells with a drug-inducible system. J Mol Cell Biol,2009,1:46-54.
[15]Liu K, Ji G, Mao J, Liu M, Wang L, Chen C, Liu L. Generation of Porcine-Induced Pluripotent Stem Cells by Using OCT4 and KLF4 Porcine Factors. Cell Reprogram,2012,14:505-513.
[16]Montserrat N, de Onate L, Garreta E, Gonzalez F, Adamo A, Eguizabal C, Hafner S, Vassena R, Izpisua Belmonte JC. Generation of feeder-free pig induced pluripotent stem cells without Pou5fl. Cell Transplant,2012,21:815-825.
[17]Kelly SJ. Studies of the developmental potential of 4-and 8-cell stage mouse blastomeres. J Exp Zool,1977,200:365-376.
[18]Yamanaka S, Blau HM. Nuclear reprogramming to a pluripotent state by three approaches. Nature, 2010,465:704-712.
[19]Yamanaka S. Strategies and new developments in the generation of patient-specific pluripotent stem cells. Cell Stem Cell,2007,1:39-49.
[20]Briggs R, King TJ. Transplantation of Living Nuclei From Blastula Cells into Enucleated Frogs' Eggs. Proc Natl Acad Sci USA,1952,38:455-463.
[21]Gurdon JB, Byrne JA. The first half-century of nuclear transplantation. Proc Natl Acad Sci USA, 2003,100:8048-8052.
[22]Bromhall JD. Nuclear transplantation in the rabbit egg. Nature,1975,258:719-722.
[23]Wilmut I, Schnieke AE, McWhir J, Kind AJ, Campbell KH. Viable offspring derived from fetal and adult mammalian cells. Cloning Stem Cells,2007,9:3-7.
[24]Hochedlinger K, Jaenisch R. Monoclonal mice generated by nuclear transfer from mature B and T donor cells. Nature,2002,415:1035-1038.
[25]Blelloch R, Wang Z, Meissner A, Pollard S, Smith A, Jaenisch R. Reprogramming efficiency following somatic cell nuclear transfer is influenced by the differentiation and methylation state of the donor nucleus. Stem Cells,2006,24:2007-2013.
[26]Wakayama T, Tabar V, Rodriguez I, Perry AC, Studer L, Mombaerts P. Differentiation of embryonic stem cell lines generated from adult somatic cells by nuclear transfer. Science,2001,292:740-743.
[27]Hochedlinger K, Jaenisch R. Nuclear transplantation, embryonic stem cells, and the potential for cell therapy. N Engl J Med,2003,349:275-286.
[28]Hwang WS, Ryu YJ, Park JH, Park ES, Lee EG, Koo JM, Jeon HY, Lee BC, Kang SK, Kim SJ, Ahn C, Hwang JH, Park KY, Cibelli JB,Moon SY. Evidence of a pluripotent human embryonic stem cell line derived from a cloned blastocyst. Science,2004,303:1669-1674.
[29]Hwang WS, Roh SI, Lee BC, Kang SK, Kwon DK, Kim S, Kim SJ, Park SW, Kwon HS, Lee CK, Lee JB, Kim JM, Ahn C, Paek SH, Chang SS, Koo JJ, Yoon HS, Hwang JH, Hwang YY, Park YS, Oh SK, Kim HS, Park JH, Moon SY, Schatten G Patient-specific embryonic stem cells derived from human SCNT blastocysts. Science,2005,308:1777-1783.
[30]Egli D, Rosains J, Birkhoff G, Eggan K. Developmental reprogramming after chromosome transfer into mitotic mouse zygotes. Nature,2007,447:679-685.
[31]Kikyo N, Wade PA, Guschin D, Ge H, Wolffe AP. Active remodeling of somatic nuclei in egg cytoplasm by the nucleosomal ATPase ISWI. Science,2000,289:2360-2362.
[32]Hansis C, Barreto G, Maltry N, Niehrs C. Nuclear reprogramming of human somatic cells by xenopus egg extract requires BRG1. Curr Biol,2004,14:1475-1480.
[33]Gonda K, Fowler J, Katoku-Kikyo N, Haroldson J, Wudel J, Kikyo N. Reversible disassembly of somatic nucleoli by the germ cell proteins FRGY2a and FRGY2b. Nat Cell Biol,2003,5:205-210.
[34]Tamada H, Van Thuan N, Reed P, Nelson D, Katoku-Kikyo N, Wudel J, Wakayama T, Kikyo N. Chromatin decondensation and nuclear reprogramming by nucleoplasmin. Mol Cell Biol,2006,26: 1259-1271.
[35]Miller RA, Ruddle FH. Pluripotent teratocarcinoma-thymus somatic cell hybrids. Cell,1976,9: 45-55.
[36]Tada M, Takahama Y, Abe K, Nakatsuji N, Tada T. Nuclear reprogramming of somatic cells by in vitro hybridization with ES cells. Curr Biol,2001,11:1553-1558.
[37]Cowan CA, Atienza J, Melton DA, Eggan K. Nuclear reprogramming of somatic cells after fusion with human embryonic stem cells. Science,2005,309:1369-1373.
[38]Yu J, Vodyanik MA, He P, Slukvin, II, Thomson JA. Human embryonic stem cells reprogram myeloid precursors following cell-cell fusion. Stem Cells,2006,24:168-176.
[39]Kimura H, Tada M, Nakatsuji N, Tada T. Histone code modifications on pluripotential nuclei of reprogrammed somatic cells. Mol Cell Biol,2004,24:5710-5720.
[40]Matsumura H, Tada M, Otsuji T, Yasuchika K, Nakatsuji N, Surani A, Tada T. Targeted chromosome elimination from ES-somatic hybrid cells. Nat Methods,2007,4:23-25.
[41]Chambers I, Colby D, Robertson M, Nichols J, Lee S, Tweedie S, Smith A. Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells. Cell,2003,113: 643-655.
[42]Mitsui K, Tokuzawa Y, Itoh H, Segawa K, Murakami M, Takahashi K, Maruyama M, Maeda M, Yamanaka S. The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells. Cell,2003,113:631-642.
[43]Taranger CK, Noer A, Sorensen AL, Hakelien AM, Boquest AC, Collas P. Induction of dedifferentiation, genomewide transcriptional programming, and epigenetic reprogramming by extracts of carcinoma and embryonic stem cells. Mol Biol Cell,2005,16:5719-5735.
[44]Do JT, Scholer HR. Nuclei of embryonic stem cells reprogram somatic cells. Stem Cells,2004,22: 941-949.
[45]Strelchenko N, Kukharenko V, Shkumatov A, Verlinsky O, Kuliev A, Verlinsky Y. Reprogramming of human somatic cells by embryonic stem cell cytoplast. Reprod Biomed Online,2006,12: 107-111.
[46]Silva J, Chambers I, Pollard S, Smith A. Nanog promotes transfer of pluripotency after cell fusion. Nature,2006,441:997-1001.
[47]Darr H, Mayshar Y, Benvenisty N. Overexpression of NANOG in human ES cells enables feeder-free growth while inducing primitive ectoderm features. Development,2006,133: 1193-1201.
[48]Hatano SY, Tada M, Kimura H, Yamaguchi S, Kono T, Nakano T, Suemori H, Nakatsuji N, Tada T. Pluripotential competence of cells associated with Nanog activity. Mech Dev,2005,122:67-79.
[49]Ivanova N, Dobrin R, Lu R, Kotenko I, Levorse J, DeCoste C, Schafer X, Lun Y, Lemischka IR. Dissecting self-renewal in stem cells with RNA interference. Nature,2006,442:533-538.
[50]Zaehres H, Lensch MW, Daheron L, Stewart SA, Itskovitz-Eldor J, Daley GQ. High-efficiency RNA interference in human embryonic stem cells. Stem Cells,2005,23:299-305.
[51]Matsui Y, Zsebo K, Hogan BL. Derivation of pluripotential embryonic stem cells from murine primordial germ cells in culture. Cell,1992,70:841-847.
[52]Jiang Y, Jahagirdar BN, Reinhardt RL, Schwartz RE, Keene CD, Ortiz-Gonzalez XR, Reyes M, Lenvik T, Lund T, Blackstad M, Du J, Aldrich S, Lisberg A, Low WC, Largaespada DA, Verfaillie CM. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature,2002,418:41-49.
[53]Kanatsu-Shinohara M, Inoue K, Lee J, Yoshimoto M, Ogonuki N, Miki H, Baba S, Kato T, Kazuki Y, Toyokuni S, Toyoshima M, Niwa O,Oshimura M, Heike T, Nakahata T, Ishino F, Ogura A, Shinohara T. Generation of pluripotent stem cells from neonatal mouse testis. Cell,2004,119: 1001-1012.
[54]Guan K, Nayernia K, Maier LS, Wagner S, Dressel R, Lee JH, Nolte J, Wolf F, Li M, Engel W, Hasenfuss G. Pluripotency of spermatogonial stem cells from adult mouse testis. Nature,2006, 440:1199-1203.
[55]Hernandez L, Kozlov S, Piras G, Stewart CL. Paternal and maternal genomes confer opposite effects on proliferation, cell-cycle length, senescence, and tumor formation. Proc Natl Acad Sci USA,2003,100:13344-13349.
[56]Allen ND, Barton SC, Hilton K, Norris ML, Surani MA. A functional analysis of imprinting in parthenogenetic embryonic stem cells. Development,1994,120:1473-1482.
[57]Cibelli JB, Grant KA, Chapman KB, Cunniff K, Worst T, Green HL, Walker SJ, Gutin PH, Vilner L, Tabar V, Dominko T, Kane J, Wettstein PJ, Lanza RP, Studer L, Vrana KE, West MD. Parthenogenetic stem cells in nonhuman primates. Science,2002,295:819.
[58]Kim K, Lerou P, Yabuuchi A, Lengerke C, Ng K, West J, Kirby A, Daly MJ, Daley GQ. Histocompatible embryonic stem cells by parthenogenesis. Science,2007,315:482-486.
[59]Maherali N, Sridharan R, Xie W, Utikal J, Eminli S, Arnold K, Stadtfeld M, Yachechko R, Tchieu J, Jaenisch R, Plath K, Hochedlinger K. Directly reprogrammed fibroblasts show global epigenetic remodeling and widespread tissue contribution. Cell Stem Cell,2007,1:55-70.
[60]Okita K, Ichisaka T, Yamanaka S. Generation of germline-competent induced pluripotent stem cells. Nature,2007,448:313-317.
[61]Wernig M, Meissner A, Foreman R, Brambrink T, Ku M, Hochedlinger K, Bernstein BE, Jaenisch R. In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature,2007,448: 318-324.
[62]Stadtfeld M, Nagaya M, Utikal J, Weir G, Hochedlinger K. Induced pluripotent stem cells generated without viral integration. Science,2008,322:945-949.
[63]Stadtfeld M, Maherali N, Breault DT, Hochedlinger K. Defining molecular cornerstones during fibroblast to iPS cell reprogramming in mouse. Cell Stem Cell,2008,2:230-240.
[64]Okita K, Nakagawa M, Hyenjong H, Ichisaka T, Yamanaka S. Generation of mouse induced pluripotent stem cells without viral vectors. Science,2008,322:949-953.
[65]Huangfu D, Maehr R, Guo W, Eijkelenboom A, Snitow M, Chen AE, Melton DA. Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds. Nat Biotechnol,2008,26:795-797.
[66]Aoi T, Yae K, Nakagawa M, Ichisaka T, Okita K, Takahashi K, Chiba T, Yamanaka S. Generation of pluripotent stem cells from adult mouse liver and stomach cells. Science,2008,321:699-702.
[67]Shi Y, Do JT, Desponts C, Hahm HS, Scholer HR, Ding S. A combined chemical and genetic approach for the generation of induced pluripotent stem cells. Cell Stem Cell,2008,2:525-528.
[68]Di Stefano B, Prigione A, Broccoli V. Efficient genetic reprogramming of unmodified somatic neural progenitors uncovers the essential requirement of Oct4 and Klf4. Stem Cells Dev,2009,18: 707-716.
[69]Takahashi K, Mitsui K, Yamanaka S. Role of ERas in promoting tumour-like properties in mouse embryonic stem cells. Nature,2003,423:541-545.
[70]Adhikary S, Eilers M. Transcriptional regulation and transformation by Myc proteins. Nat Rev Mol Cell Biol,2005,6:635-645.
[71]Rowland BD, Bernards R, Peeper DS. The KLF4 tumour suppressor is a transcriptional repressor of p53 that acts as a context-dependent oncogene. Nat Cell Biol,2005,7:1074-1082.
[72]Meshorer E, Yellajoshula D, George E, Scambler PJ, Brown DT, Misteli T. Hyperdynamic plasticity of chromatin proteins in pluripotent embryonic stem cells. Dev Cell,2006,10:105-116.
[73]Knoepfler PS, Zhang XY, Cheng PF, Gafken PR, McMahon SB, Eisenman RN. Myc influences global chromatin structure. EMBO J,2006,25:2723-2734.
[74]Nakatake Y, Fukui N, Iwamatsu Y, Masui S, Takahashi K, Yagi R, Yagi K, Miyazaki J, Matoba R, Ko MS, Niwa H. Klf4 cooperates with Oct3/4 and Sox2 to activate the Leftyl core promoter in embryonic stem cells. Mol Cell Biol,2006,26:7772-7782.
[75]Masui S, Nakatake Y, Toyooka Y, Shimosato D, Yagi R, Takahashi K, Okochi H, Okuda A, Matoba R, Sharov AA, Ko MS, Niwa H. Pluripotency governed by Sox2 via regulation of Oct3/4 expression in mouse embryonic stem cells. Nat Cell Biol,2007,9:625-635.
[76]Hochedlinger K, Yamada Y, Beard C, Jaenisch R. Ectopic expression of Oct-4 blocks progenitor-cell differentiation and causes dysplasia in epithelial tissues. Cell,2005,121:465-477.
[77]Boyer LA, Plath K, Zeitlinger J, Brambrink T, Medeiros LA, Lee TI, Levine SS, Wernig M, Tajonar A, Ray MK, Bell GW, Otte AP, Vidal M,Gifford DK, Young RA, Jaenisch R. Polycomb complexes repress developmental regulators in murine embryonic stem cells. Nature,2006,441:349-353.
[78]Niwa H, Miyazaki J, Smith AG. Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells. Nat Genet,2000,24:372-376.
[79]Zhou S, Ding C, Zhao X, Wang E, Dai X, Liu L, Li W, Liu Z, Wan H, Feng C, Hai T, Wang L, Zhou Q. Successful generation of cloned mice using nuclear transfer from induced pluripotent stem cells. Cell Res,2010,20:850-853.
[80]Kaji K, Norrby K, Paca A, Mileikovsky M, Mohseni P, Woltjen K. Virus-free induction of pluripotency and subsequent excision of reprogramming factors. Nature,2009,458:771-775.
[81]Woltjen K, Michael IP, Mohseni P, Desai R, Mileikovsky M, Hamalainen R, Cowling R, Wang W, Liu P, Gertsenstein M, Kaji K, Sung HK, Nagy A. piggyBac transposition reprograms fibroblasts to induced pluripotent stem cells. Nature,2009,458:766-770.
[82]Yu J, Hu K, Smuga-Otto K, Tian S, Stewart R, Slukvin Ⅱ, Thomson JA. Human induced pluripotent stem cells free of vector and transgene sequences. Science,2009,324:797-801.
[83]Huangfu D, Osafune K, Maehr R, Guo W, Eijkelenboom A, Chen S, Muhlestein W, Melton DA. Induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2. Nat Biotechnol,2008,26:1269-1275.
[84]Marson A, Levine SS, Cole MF, Frampton GM, Brambrink T, Johnstone S, Guenther MG, Johnston WK, Wernig M, Newman J,Calabrese JM, Dennis LM, Volkert TL, Gupta S, Love J, Hannett N, Sharp PA, Bartel DP, Jaenisch R, Young RA. Connecting microRNA genes to the core transcriptional regulatory circuitry of embryonic stem cells. Cell,2008,134:521-533.
[85]Shi Y, Desponts C, Do JT, Hahm HS, Scholer HR, Ding S. Induction of pluripotent stem cells from mouse embryonic fibroblasts by Oct4 and Klf4 with small-molecule compounds. Cell Stem Cell, 2008,3:568-574.
[86]Meissner A, Wernig M, Jaenisch R. Direct reprogramming of genetically unmodified fibroblasts into pluripotent stem cells. Nat Biotechnol,2007,25:1177-1181.
[87]Okamoto K, Okazawa H, Okuda A, Sakai M, Muramatsu M, Hamada H. A novel octamer binding transcription factor is differentially expressed in mouse embryonic cells. Cell,1990,60:461-472.
[88]Rosner MH, Vigano MA, Ozato K, Timmons PM, Poirier F, Rigby PW, Staudt LM. A POU-domain transcription factor in early stem cells and germ cells of the mammalian embryo. Nature,1990,345: 686-692.
[89]Scholer HR, Ruppert S, Suzuki N, Chowdhury K, Gruss P. New type of POU domain in germ line-specific protein Oct-4. Nature,1990,344:435-439.
[90]Nichols J, Zevnik B, Anastassiadis K, Niwa H, Klewe-Nebenius D, Chambers I, Scholer H, Smith A. Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4. Cell,1998,95:379-391.
[91]Shimozaki K, Nakashima K, Niwa H, Taga T. Involvement of Oct3/4 in the enhancement of neuronal differentiation of ES cells in neurogenesis-inducing cultures. Development,2003,130: 2505-2512.
[92]Zeineddine D, Papadimou E, Chebli K, Gineste M, Liu J, Grey C, Thurig S, Behfar A, Wallace VA, Skerjanc IS, Puceat M. Oct-3/4 dose dependently regulates specification of embryonic stem cells toward a cardiac lineage and early heart development. Dev Cell,2006,11:535-546.
[93]Yuan H, Corbi N, Basilico C, Dailey L. Developmental-specific activity of the FGF-4 enhancer requires the synergistic action of Sox2 and Oct-3. Genes Dev,1995,9:2635-2645.
[94]Avilion AA, Nicolis SK, Pevny LH, Perez L, Vivian N, Lovell-Badge R. Multipotent cell lineages in early mouse development depend on SOX2 function. Genes Dev,2003,17:126-140.
[95]Li M, Pevny L, Lovell-Badge R, Smith A. Generation of purified neural precursors from embryonic stem cells by lineage selection. Curr Biol,1998,8:971-974.
[96]Zappone MV, Galli R, Catena R,Meani N, De Biasi S,Mattei E,Tiveron C, Vescovi AL, Lovell-Badge R, Ottolenghi S, Nicolis SK. Sox2 regulatory sequences direct expression of a (beta)-geo transgene to telencephalic neural stem cells and precursors of the mouse embryo, revealing regionalization of gene expression in CNS stem cells. Development,2000,127: 2367-2382.
[97]Kamachi Y, Uchikawa M, Kondoh H. Pairing SOX off:with partners in the regulation of embryonic development. Trends Genet,2000,16:182-187.
[98]Wilson M, Koopman P, Matching SOX:partner proteins and co-factors of the SOX family of transcriptional regulators. Curr Opin Genet Dev,2002,12:441-446.
[99]Nishimoto M, Miyagi S, Katayanagi T, Tomioka M, Muramatsu M, Okuda A. The embryonic Octamer factor 3/4 displays distinct DNA binding specificity from those of other Octamer factors. Biochem Biophys Res Commun,2003,302:581-586.
[100]Tokuzawa Y, Kaiho E, Marayama M, Takahashi K, Mitsui K, Maeda M, Niwa H, Yamanaka S. Fbx15 is a novel target of Oct3/4 but is dispensable for embryonic stem cell self-renewal and mouse development. Mol Cell Biol,2003,23:2699-2708.
[101]Chew JL, Loh YH, Zhang W, Chen X, Tam WL, Yeap LS, Li P, Ang YS, Lim B, Robson P, Ng HH. Reciprocal transcriptional regulation of Pou5fl and Sox2 via the Oct4/Sox2 complex in embryonic stem cells. Mol Cell Biol,2005,25:6031-6046.
[102]Okumura-Nakanishi S, Saito M, Niwa H, Ishikawa F. Oct-3/4 and Sox2 regulate Oct-3/4 gene in embryonic stem cells. J Biol Chem,2005,280:5307-5317.
[103]Tomioka M, Nishimoto M, Miyagi S, Katayanagi T, Fukui N, Niwa H, Muramatsu M, Okuda A. Identification of Sox-2 regulatory region which is under the control of Oct-3/4-Sox-2 complex. Nucleic Acids Res,2002,30:3202-3213.
[104]Kuroda T, Tada M, Kubota H, Kimura H, Hatano SY, Suemori H, Nakatsuji N, Tada T. Octamer and Sox elements are required for transcriptional cis regulation of Nanog gene expression. Mol Cell Biol,2005,25:2475-2485.
[105]Rodda DJ, Chew JL, Lim LH, Loh YH, Wang B, Ng HH, Robson P. Transcriptional regulation of nanog by OCT4 and SOX2. J Biol Chem,2005,280:24731-24737.
[106]Boyer LA, Lee TI, Cole MF, Johnstone SE, Levine SS, Zucker JP, Guenther MG, Kumar RM, Murray HL, Jenner RG, Gifford DK, Melton DA, Jaenisch R, Young RA. Core transcriptional regulatory circuitry in human embryonic stem cells. Cell,2005,122:947-956.
[107]Loh YH, Wu Q, Chew JL, Vega VB, Zhang W, Chen X, Bourque G, George J, Leong B, Liu J, Wong KY, Sung KW, Lee CW, Zhao XD,Chiu KP, Lipovich L, Kuznetsov VA, Robson P, Stanton LW, Wei CL, Ruan Y, Lim B, Ng HH. The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells. Nat Genet,2006,38:431-440.
[108]Dalla-Favera R, Bregni M, Erikson J, Patterson D, Gallo RC, Croce CM. Human c-myc one gene is located on the region of chromosome 8 that is translocated in Burkitt lymphoma cells. Proc Natl Acad Sci USA,1982,79:7824-7827.
[109]Davis AC, Wims M, Spotts GD, Hann SR, Bradley A. A null c-myc mutation causes lethality before 10.5 days of gestation in homozygotes and reduced fertility in heterozygous female mice. Genes Dev,1993,7:671-682.
[110]Baudino TA, McKay C, Pendeville-Samain H, Nilsson JA, Maclean KH, White EL, Davis AC, Ihle JN, Cleveland JL. c-Myc is essential for vasculogenesis and angiogenesis during development and tumor progression. Genes Dev,2002,16:2530-2543.
[111]Cartwright P, McLean C, Sheppard A, Rivett D, Jones K, Dalton S. LIF/STAT3 controls ES cell self-renewal and pluripotency by a Myc-dependent mechanism. Development,2005,132: 885-896.
[112]Cawley S, Bekiranov S, Ng HH, Kapranov P, Sekinger EA, Kampa D, Piccolboni A, Sementchenko V, Cheng J, Williams AJ, Wheeler R, Wong B, Drenkow J, Yamanaka M, Patel S, Brubaker S, Tammana H, Helt G, Struhl K, Gingeras TR. Unbiased mapping of transcription factor binding sites along human chromosomes 21 and 22 points to widespread regulation of noncoding RNAs. Cell,2004,116:499-509.
[113]Fernandez PC, Frank SR, Wang L, Schroeder M, Liu S, Greene J, Cocito A, Amati B. Genomic targets of the human c-Myc protein. Genes Dev,2003,17:1115-1129.
[114]Li Z, Van Calcar S, Qu C, Cavenee WK, Zhang MQ, Ren B. A global transcriptional regulatory role for c-Myc in Burkitt's lymphoma cells. Proc Natl Acad Sci USA,2003,100:8164-8169.
[115]Grandori C, Wu KJ, Fernandez P, Ngouenet C, Grim J, Clurman BE, Moser MJ, Oshima J, Russell DW, Swisshelm K, Frank S, Amati B,Dalla-Favera R, Monnat RJ Jr. Werner syndrome protein limits MYC-induced cellular senescence. Genes Dev,2003,17:1569-1574.
[116]Peukert K, Staller P, Schneider A, Carmichael G, Hanel F, Eilers M. An alternative pathway for gene regulation by Myc. EMBO J,1997,16:5672-5686.
[117]O'Donnell KA, Wentzel EA, Zeller KI, Dang CV, Mendell JT. c-Myc-regulated microRNAs modulate E2F1 expression. Nature,2005,435:839-843.
[118]Schuh R, Aicher W, Gaul U, Cote S, Preiss A, Maier D, Seifert E, Nauber U, Schroder C, Kemler R. A conserved family of nuclear proteins containing structural elements of the finger protein encoded by Kruppel, a Drosophila segmentation gene. Cell,1986,47:1025-1032.
[119]Garrett-Sinha LA, Eberspaecher H, Seldin MF, de Crombrugghe B. A gene for a novel zinc-finger protein expressed in differentiated epithelial cells and transiently in certain mesenchymal cells. J Biol Chem,1996,271:31384-31390.
[120]Shields JM, Christy RJ, Yang VW. Identification and characterization of a gene encoding a gut-enriched Kruppel-like factor expressed during growth arrest. J Biol Chem,1996,271: 20009-20017.
[121]Chen X, Johns DC, Geiman DE, Marban E, Dang DT, Hamlin G, Sun R, Yang VW. Kruppel-like factor 4 (gut-enriched Kruppel-like factor) inhibits cell proliferation by blocking G1/S progression of the cell cycle. J Biol Chem,2001,276:30423-30428.
[122]Segre JA, Bauer C, Fuchs E. K1f4 is a transcription factor required for establishing the barrier function of the skin. Nat Genet,1999,22:356-360.
[123]Katz JP, Perreault N, Goldstein BG, Lee CS, Labosky PA, Yang VW, Kaestner KH. The zinc-finger transcription factor Klf4 is required for terminal differentiation of goblet cells in the colon. Development,2002,129:2619-2628.
[124]Katz JP, Perreault N, Goldstein BG, Actman L, McNally SR, Silberg DG, Furth EE, Kaestner KH. Loss of Klf4 in mice causes altered proliferation and differentiation and precancerous changes in the adult stomach. Gastroenterology,2005,128:935-945.
[125]Foster KW, Frost AR, McKie-Bell P, Lin CY, Engler JA, Grizzle WE, Ruppert JM. Increase of GKLF messenger RNA and protein expression during progression of breast cancer. Cancer Res, 2000,60:6488-6495.
[126]Foster KW, Ren S, Louro ID, Lobo-Ruppert SM, McKie-Bell P, Grizzle W, Hayes MR, Broker TR, Chow LT, Ruppert JM. Oncogene expression cloning by retroviral transduction of adenovirus E1A-immortalized rat kidney RK3E cells:transformation of a host with epithelial features by c-MYC and the zinc finger protein GKLF. Cell Growth Differ,1999,10:423-434.
[127]Foster KW, Liu Z, Nail CD, Li X, Fitzgerald TJ, Bailey SK, Frost AR, Louro ID, Townes TM, Paterson AJ, Kudlow JE, Lobo-Ruppert SM,Ruppert JM. Induction of KLF4 in basal keratinocytes blocks the proliferation-differentiation switch and initiates squamous epithelial dysplasia. Oncogene,2005,24:1491-1500.
[128]Rowland BD, Peeper DS. KLF4, p21 and context-dependent opposing forces in cancer. Nat Rev Cancer,2006,6:11-23.
[129]Li Y, McClintick J, Zhong L, Edenberg HJ, Yoder MC, Chan RJ. Murine embryonic stem cell differentiation is promoted by SOCS-3 and inhibited by the zinc finger transcription factor K1f4. Blood,2005,105:635-637.
[130]Loh YH, Ng JH, Ng HH. Molecular framework underlying pluripotency. Cell Cycle,2008,7: 885-891.
[131]Amabile G, Meissner A. Induced pluripotent stem cells:current progress and potential for regenerative medicine. Trends Mol Med,2009,15:59-68.
[132]Viswanathan SR, Daley GQ, Gregory RI. Selective blockade of microRNA processing by Lin28. Science,2008,320:97-100.
[133]Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM. Embryonic stem cell lines derived from human blastocysts. Science,1998,282:1145-1147.
[134]Hanna J, Wernig M, Markoulaki S, Sun CW, Meissner A, Cassady JP, Beard C, Brambrink T, Wu LC, Townes TM, Jaenisch R. Treatment of sickle cell anemia mouse model with iPS cells generated from autologous skin. Science,2007,318:1920-1923.
[135]Saporta MA. Grskovic M, Dimos JT. Induced pluripotent stem cells in the study of neurological diseases. Stem Cell Res Ther,2011,5:37.
[136]Mauritz C, Schwanke K, Reppel M, Neef S, Katsirntaki K, Maier LS, Nguemo F, Menke S, Haustein M, Hescheler J, Hasenfuss G, Martin U. Generation of functional murine cardiac myocytes from induced pluripotent stem cells. Circulation,2008,118:507-517.
[137]Narazaki G, Uosaki H, Teranishi M, Okita K, Kim B, Matsuoka S, Yamanaka S, Yamashita JK. Directed and systematic differentiation of cardiovascular cells from mouse induced pluripotent stem cells. Circulation,2008,118:498-506.
[138]Chamberlain SJ, Li XJ, Lalande M. Induced pluripotent stem (iPS) cells as in vitro models of human neurogenetic disorders. Neurogenetics,2008,9:227-235.
[139]Xu D, Alipio Z, Fink LM, Adcock DM, Yang J, Ward DC, Ma Y. Phenotypic correction of murine hemophilia A using an iPS cell-based therapy. Proc Natl Acad Sci USA,2009,106:808-813.
[140]Nakagawa M, Koyanagi M, Tanabe K, Takahashi K, Ichisaka T, Aoi T, Okita K, Mochiduki Y, Takizawa N, Yamanaka S. Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nat Biotechnol,200826:101-106.
[141]Gurdon J, Murdoch A. Nuclear transfer and iPS may work best together. Cell Stem Cell,2008,2: 135-138.
[142]Brambrink T, Foreman R, Welstead GG, Lengner CJ, Wernig M, Suh H, Jaenisch R. Sequential expression of pluripotency markers during direct reprogramming of mouse somatic cells. Cell Stem Cell,2008,2:151-159.
[143]McCormack MP, Rabbitts TH. Activation of the T-cell oncogene LMO2 after gene therapy for X-linked severe combined immunodeficiency. N Engl J Med,2004,350:913-922.
[144]Raper SE, Chirmule N, Lee FS, Wivel NA, Bagg A, Gao GP, Wilson JM, Batshaw ML. Fatal systemic inflammatory response syndrome in a ornithine transcarbamylase deficient patient following adenoviral gene transfer. Mol Genet Metab,2003,80:148-158.
[145]Hacein-Bey-Abina S,Le Deist F, Carlier F, Bouneaud C,Hue C,De Villartay JP, Thrasher AJ, Wulffraat N, Sorensen R, Dupuis-Girod S,Fischer A, Davies EG, Kuis W, Leiva L, Cavazzana-Calvo M. Sustained correction of X-linked severe combined immunodeficiency by ex vivo gene therapy. N Engl J Med,2002,346:1185-1193.
[146]Hacein-Bey-Abina S, von Kalle C, Schmidt M, Le Deist F, Wulffraat N, McIntyre E, Radford I, Villeval JL, Fraser CC, Cavazzana-Calvo M,Fischer A. A serious adverse event after successful gene therapy for X-linked severe combined immunodeficiency. N Engl J Med,2003,348: 255-256.
[147]Rideout WM,3rd, Hochedlinger K, Kyba M, Daley GQ, Jaenisch R. Correction of a genetic defect by nuclear transplantation and combined cell and gene therapy. Cell,2002,109:17-27.
[148]Narayan AD, Chase JL, Lewis RL, Tian X, Kaufman DS, Thomson JA, Zanjani ED. Human embryonic stem cell-derived hematopoietic cells are capable of engrafting primary as well as secondary fetal sheep recipients. Blood,2006,107:2180-2183.
[149]Takagi Y, Takahashi J, Saiki H, Morizane A, Hayashi T, Kishi Y, Fukuda H, Okamoto Y, Koyanagi M, Ideguchi M, Hayashi H, Imazato T,Kawasaki H, Suemori H, Omachi S, Iida H, Itoh N, Nakatsuji N, Sasai Y, Hashimoto N. Dopaminergic neurons generated from monkey embryonic stem cells function in a Parkinson primate model. J Clin Invest,2005,115:102-109.
[150]Ishii T, Yasuchika K, Machimoto T, Kamo N, Komori J, Konishi S, Suemori H, Nakatsuji N, Saito M, Kohno K, Uemoto S, Ikai I. Transplantation of embryonic stem cell-derived endodermal cells into mice with induced lethal liver damage. Stem Cells,2007,25:3252-3260.
[151]Leor J, Gerecht S, Cohen S, Miller L, Holbova R, Ziskind A, Shachar M, Feinberg MS, Guetta E, Itskovitz-Eldor J. Human embryonic stem cell transplantation to repair the infarcted myocardium. Heart,2007,93:1278-1284.
[152]Boyd AS, Wu DC, Higashi Y, Wood KJ. A comparison of protocols used to generate insulin-producing cell clusters from mouse embryonic stem cells. Stem Cells,2008,26: 1128-1137.
[153]Evans MJ, Kaufman MH. Establishment in culture of pluripotential cells from mouse embryos. Nature,1981,292:154-156.
[154]Alberio R, Croxall N, Allegrucci C. Pig epiblast stem cells depend on activin/nodal signaling for pluripotency and self-renewal. Stem Cells Dev,2010,19:1627-1636.
[155]West FD, Terlouw SL, Kwon DJ, Mumaw JL, Dhara SK, Hasneen K, Dobrinsky JR, Stice SL. Porcine induced pluripotent stem cells produce chimeric offspring. Stem Cells Dev,2010,19: 1211-1220.
[156]West FD, Uhl EW, Liu Y, Stowe H, Lu Y, Yu P, Gallegos-Cardenas A, Pratt SL, Stice SL. Brief report:chimeric pigs produced from induced pluripotent stem cells demonstrate germline transmission and no evidence of tumor formation in young pigs. Stem Cells,2011,29:1640-1643.
[157]Zhou L, Wang W, Liu Y, Fernandez de Castro J, Ezashi T, Telugu BP, Roberts RM, Kaplan HJ, Dean DC. Differentiation of induced pluripotent stem cells of swine into rod photoreceptors and their integration into the retina. Stem Cells,2011,29:972-980.
[158]Telugu BP, Ezashi T, Roberts RM. Porcine induced pluripotent stem cells analogous to naive and primed embryonic stem cells of the mouse. Int J Dev Biol,2010,54:1703-1713.
[159]Sumer H, Liu J, Malaver-Ortega LF, Lim ML, Khodadadi K, Verma PJ. NANOG is a key factor for induction of pluripotency in bovine adult fibroblasts. J Anim Sci,2011,89:2708-2716.
[160]Sartori C, DiDomenico A I, Thomson AJ, Milne E, Lillico SG, Burdon TG, Whitelaw CB. Ovine-induced pluripotent stem cells can contribute to chimeric lambs. Cell Reprogram,2012,14: 8-19.
[161]Keefer CL, Pant D, Blomberg L, Talbot NC. Challenges and prospects for the establishment of embryonic stem cell lines of domesticated ungulates. Anim Reprod Sci,2007,98:147-168.
[162]Piedrahita J A, Moore K, Lee C, Oetama B, Weaks R, Ramsoondar J, Thomson J, Vasquez J. Advances in the generation of transgenic pigs via embryo-derived and primordial germ cell-derived cells. J Reprod Fertil Suppl,1997,52:245-254.
[163]Shim H, Gutierrez-Adan A, Chen LR, BonDurant RH, Behboodi E, Anderson GB. Isolation of pluripotent stem cells from cultured porcine primordial germ cells. Biol Reprod,1997,57: 1089-1095.
[164]Mueller S, Prelle K, Rieger N, Petznek H, Lassnig C, Luksch U,Aigner B, Baetscher M, Wolf E, Mueller M, Brem G. Chimeric pigs following blastocyst injection of transgenic porcine primordial germ cells. Mol Reprod Dev,1999,54:244-254.
[165]Tsung HC, Du ZW, Rui R, Li XL, Bao LP, Wu J, Bao SM, Yao Z. The culture and establishment of embryonic germ (EG) cell lines from Chinese mini swine. Cell Res,2003,13:195-202.
[166]Rui R, Shim H, Moyer AL, Anderson DL, Penedo CT, Rowe JD, BonDurant RH, Anderson GB. Attempts to enhance production of porcine chimeras from embryonic germ cells and preimplantation embryos. Theriogenology,2004,61:1225-1235.
[167]Kastenberg ZJ, Odorico JS. Alternative sources of pluripotency:science, ethics, and stem cells. Transplant Rev (Orlando),2008,22:215-222.
[168]Lu HE,Tsai MS, Yang YC,Yuan CC, Wang TH, Lin XZ, Tseng CP, Hwang SM. Selection of alkaline phosphatase-positive induced pluripotent stem cells from human amniotic fluid-derived cells by feeder-free system. Exp Cell Res,2011,317:1895-1903.
[169]Notarianni E, Galli C, Laurie S, Moor RM, Evans MJ. Derivation of pluripotent, embryonic cell lines from the pig and sheep. J Reprod Fertil Suppl,1991,43:255-260.
[170]Kirchhof N, Carnwath JW, Lemme E, Anastassiadis K, Scholer H, Niemann H. Expression pattern of Oct-4 in preimplantation embryos of different species. Biol Reprod,2000,63:1698-1705.
[171]Vejlsted M, Avery B, Schmidt M, Greve T, Alexopoulos N, Maddox-Hyttel P. Ultrastructural and immunohistochemical characterization of the bovine epiblast. Biol Reprod,2005,72:678-686.
[172]Rodriguez A, De Frutos C, Diez C, Caamano JN, Facal N, Duque P, Garcia-Ochoa C, G6mez E. Effects of human versus mouse leukemia inhibitory factor on the in vitro development of bovine embryos. Theriogenology,2007,67:1092-1095.
[173]Eggenschwiler R, Cantz T. Induced pluripotent stem cells generated without viral integration. Hepatology,2009,49:1048-1049.
[174]Fusaki N, Ban H, Nishiyama A, Saeki K, Hasegawa M. Efficient induction of transgene-free human pluripotent stem cells using a vector based on Sendai virus, an RNA virus that does not integrate into the host genome. Proc Jpn Acad Ser B Phys Biol Sci,2009,85:348-362.
[175]Talbot NC, Blomberg Le A. The pursuit of ES cell lines of domesticated ungulates. Stem Cell Rev, 2008,4:235-254.
[176]Wan YJ, Zhang YL, Zhou ZR, Jia RX, Li M, Song H, Wang ZY, Wang LZ, Zhang GM, You JH, Wang F. Efficiency of donor cell preparation and recipient oocyte source for production of transgenic cloned dairy goats harboring human lactoferrin. Theriogenology,2012,78:583-592.
[177]Maherali N, Ahfeldt T, Rigamonti A, Utikal J, Cowan C, Hochedlinger K. A high-efficiency system for the generation and study of human induced pluripotent stem cells. Cell Stem Cell,2008, 3:340-345.
[178]Fan N, Chen J, Shang Z, Dou H, Ji G, Zou Q, Wu L, He L, Wang F, Liu K, Liu N, Han J, Zhou Q, Pan D, Yang D, Zhao B, Ouyang Z, Liu Z,Zhao Y, Lin L, Zhong C, Wang Q, Wang S, Xu Y, Luan J, Liang Y, Yang Z, Li J, Lu C, Vajta G, Li Z, Ouyang H, Wang H, Wang Y, Yang Y,Liu Z, Wei H, Luan Z, Esteban MA, Deng H, Yang H, Pei D, Li N, Pei G, Liu L, Du Y, Xiao L, Lai L. Piglets cloned from induced pluripotent stem cells. Cell Res,2013,23:162-166.
[179]Kou Z, Kang L, Yuan Y, Tao Y, Zhang Y, Wu T, He J, Wang J, Liu Z, Gao S. Mice cloned from induced pluripotent stem cells (iPSCs). Biol Reprod,2010,83:238-243.
[180]Wilmut I, Beaujean N, de Sousa PA, Dinnyes A, King TJ,Paterson LA, Wells DN, Young LE. Somatic cell nuclear transfer. Nature,2002,419:583-586.
[181]Rideout WM 3rd, Wakayama T, Wutz A, Eggan K, Jackson-Grusby L, Dausman J, Yanagimachi R, Jaenisch R. Generation of mice from wild-type and targeted ES cells by nuclear cloning. Nat Genet,2000,24:109-110.
[182]Keefer CL. Production of bioproducts through the use of transgenic animal models. Anim Reprod Sci,2004,82-83:5-12.
[183]Donovan DM, Kerr DE, Wall RJ. Engineering disease resistant cattle. Transgenic Res,2005,14: 563-567.
[184]Wall RJ, Powell AM, Paape MJ, Kerr DE, Bannerman DD, Pursel VG, Wells KD, Talbot N, Hawk HW. Genetically enhanced cows resist intramammary Staphylococcus aureus infection. Nat Biotechnol,2005,23:445-451.
[185]Bavister B. The role of animal studies in supporting human assisted reproductive technology. Reprod Fertil Dev,2004,16:719-728.
[186]Ohgane J, Wakayama T, Senda S, Yamazaki Y, Inoue K, Ogura A, Marh J, Tanaka S, Yanagimachi R, Shiota K. The Sall3 locus is an epigenetic hotspot of aberrant DNA methylation associated with placentomegaly of cloned mice. Genes Cells,2004,9:253-260.
[187]Kang YK, Koo DB, Park JS, Choi YH, Chung AS, Lee KK, Han YM. Aberrant methylation of donor genome in cloned bovine embryos. Nat Genet,2001,28:173-177.
[188]Santos F, Zakhartchenko V, Stojkovic M, Peters A, Jenuwein T, Wolf E, Reik W, Dean W. Epigenetic marking correlates with developmental potential in cloned bovine preimplantation embryos. Curr Biol,2003,13:1116-1121.
[189]Dean W, Santos F, Stojkovic M, Zakhartchenko V, Walter J, Wolf E, Reik W. Conservation of methylation reprogramming in mammalian development:aberrant reprogramming in cloned embryos. Proc Natl Acad Sci USA,2001,98:13734-13738.
[190]Kishigami S, Mizutani E, Ohta H, Hikichi T, Thuan NV, Wakayama S, Bui HT, Wakayama T. Significant improvement of mouse cloning technique by treatment with trichostatin A after somatic nuclear transfer. Biochem Biophys Res Commun,2006,340:183-189.
[191]Balasubramanian S, Babai N, Chaudhuri A, Qiu F, Bhattacharya S, Dave BJ, Parameswaran S, Carson SD, Thoreson WB, Sharp JG,Rao M, Ahmad I. Non cell-autonomous reprogramming of adult ocular progenitors:generation of pluripotent stem cells without exogenous transcription factors. Stem Cells,2009,27:3053-3062.
[192]Kim JB, Greber B, Arauzo-Bravo MJ, Meyer J, Park KI, Zaehres H, Scholer HR. Direct reprogramming of human neural stem cells by OCT4. Nature,2009461:649-643.
[193]Li W, Zhou H, Abujarour R, Zhu S, Young Joo J, Lin T, Hao E, Scholer HR, Hayek A, Ding S. Generation of human-induced pluripotent stem cells in the absence of exogenous Sox2. Stem Cells, 2009,27:2992-3000.
[194]Aasen T, Raya A, Barrero MJ, Garreta E, Consiglio A, Gonzalez F, Vassena R, Bilic J, Pekarik V, Tiscornia G, Edel M, Boue S, Izpisua Belmonte JC. Efficient and rapid generation of induced pluripotent stem cells from human keratinocytes. Nat Biotechnol,2008,26:1276-1284.
[195]Tan KY, Eminli S, Hettmer S, Hochedlinger K, Wagers AJ. Efficient generation of iPS cells from skeletal muscle stem cells. PLoS One,2011,6:e26406.
[196]Hiratsuka M, Uno N, Ueda K, Kurosaki H, Imaoka N, Kazuki K, Ueno E, Akakura Y, Katoh M, Osaki M, Kazuki Y, Nakagawa M, Yamanaka S, Oshimura M. Integration-free iPS cells engineered using human artificial chromosome vectors. PLoS One,2011,6:e25961.
[197]Kane NM, Nowrouzi A, Mukherjee S, Blundell MP, Greig JA, Lee WK, Houslay MD, Milligan G, Mountford JC, von Kalle C, Schmidt M,Thrasher AJ, Baker AH. Lentivirus-mediated reprogramming of somatic cells in the absence of transgenic transcription factors. Mol Ther,2010, 18:2139-2145.
[198]Ralston A, Rossant J. Genetic regulation of stem cell origins in the mouse embryo. Clin Genet, 2005,68:106-112.
[199]Beddington RS, Robertson EJ. An assessment of the developmental potential of embryonic stem cells in the midgestation mouse embryo. Development,1989,105:733-737.
[200]Yaseen MA, Wrenzycki C, Herrmann D, Carnwath JW, Niemann H. Changes in the relative abundance of mRNA transcripts for insulin-like growth factor (IGF-I and IGF-II) ligands and their receptors (IGF-IR/IGF-IIR) in preimplantation bovine embryos derived from different in vitro systems. Reproduction,2001,122:601-610.
[201]Pandey A, Singh N, Gupta SC, Rana JS, Gupta N. Relative expression of cell growth regulatory genes insulin-like growth factors (IGF-1 and IGF-2) and their receptors (IGF-1R and IGF-2R) in somatic cell nuclear transferred (SCNT) and in vitro fertilized (IVF) pre-implantation buffalo embryos. Cell Biol Int,2009,33:555-564.
[202]Kim S, Lee GS, Lee SH, Kim HS, Jeong YW, Kim JH, Kang SK, Lee BC, Hwang WS. Embryotropic effect of insulin-like growth factor (IGF)-I and its receptor on development of porcine preimplantation embryos produced by in vitro fertilization and somatic cell nuclear transfer. Mol Reprod Dev,2005,72:88-97.
[203]Kim S, Lee SH, Kim JH, Jeong YW, Hashem MA, Koo OJ, Park SM, Lee EG, Hossein MS, Kang SK, Lee BC, Hwang WS. Anti-apoptotic effect of insulin-like growth factor (IGF)-I and its receptor in porcine preimplantation embryos derived from in vitro fertilization and somatic cell nuclear transfer. Mol Reprod Dev,2006,73:1523-1530.
[204]Miyoshi K, Mori H, Mizobe Y, Akasaka E, Ozawa A, Yoshida M, Sato M. Valproic acid enhances in vitro development and Oct-3/4 expression of miniature pig somatic cell nuclear transfer embryos. Cell Reprogram,2010,12:67-74.
[205]Han DW, Song SJ, Uhum SJ, Do JT, Kim NH, Chung KS, Lee HT. Expression of IGF2 and IGF receptor mRNA in bovine nuclear transferred embryos. Zygote,2003,11:245-252.
[206]Schultz GA, Hogan A, Watson AJ, Smith RM, Heyner S. Insulin, insulin-like growth factors and glucose transporters:temporal patterns of gene expression in early murine and bovine embryos. Reprod Fertil Dev,1992,4:361-371.
[207]Watson AJ, Hogan A, Hahnel A, Wiemer KE, Schultz GA. Expression of growth factor ligand and receptor genes in the preimplantation bovine embryo. Mol Reprod Dev,1992,31:87-95.
[208]Doherty AS, Temeles GL, Schultz RM. Temporal pattern of IGF-I expression during mouse preimplantation embryogenesis. Mol Reprod Dev,1994,37:21-26.
[209]Yoshida Y, Miyamura M, Hamano S, Yoshida M. Expression of growth factor ligand and their receptor mRNAs in bovine ova during in vitro maturation and after fertilization in vitro. J Vet Med Sci,1998,60:549-554.
[210]Lonergan P, Gutierrez-Adan A, Pintado B, Fair T, Ward F, Fuente JD, Boland M. Relationship between time of first cleavage and the expression of IGF-I growth factor, its receptor, and two housekeeping genes in bovine two-cell embryos and blastocysts produced in vitro. Mol Reprod Dev,2000,57:146-152.
[211]Rappolee DA, Sturm KS, Behrendtsen O, Schultz GA, Pedersen RA, Werb Z. Insulin-like growth factor Ⅱ acts through an endogenous growth pathway regulated by imprinting in early mouse embryos. Genes Dev,1992,6:939-952.
[212]Zhang X, Kidder GM, Watson AJ, Schultz GA, Armstrong DT. Possible roles of insulin and insulin-like growth factors in rat preimplantation development:investigation of gene expression by reverse transcription-polymerase chain reaction. J Reprod Fertil,1994,100:375-380.
[213]Daliri M, Rao KB, Kaur G, Garg S, Patil S, Totey SM. Expression of growth factor ligand and receptor genes in preimplantation stage water buffalo (Bubalus bubalis) embryos and oviduct epithelial cells. J Reprod Fertil,1999,117:61-70.
[214]Lighten AD, Hardy K, Winston RM, Moore GE. Expression of mRNA for the insulin-like growth factors and their receptors in human preimplantation embryos. Mol Reprod Dev,1997,47: 134-139.
[2]Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell,2007,131:861-872.
[3]Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie J, Jonsdottir GA, Ruotti V, Stewart R, Slukvin Ⅱ, Thomson JA. Induced pluripotent stem cell lines derived from human somatic cells. Science,2007,318:1917-1920.
[4]Ren J, Pak Y, He L, Qian L, Gu Y, Li H, Rao L, Liao J, Cui C, Xu X, Zhou J, Ri H, Xiao L. Generation of hircine-induced pluripotent stem cells by somatic cell reprogramming. Cell Res,2011, 21:849-853.
[5]Bao L, He L, Chen J, Wu Z, Liao J, Rao L, Ren J, Li H, Zhu H, Qian L, Gu Y, Dai H, Xu X, Zhou J, Wang W, Cui C, Xiao L. Reprogramming of ovine adult fibroblasts to pluripotency via drug-inducible expression of defined factors. Cell Res,2011,21:600-608.
[6]Li Y, Cang M, Lee AS, Zhang K, Liu D. Reprogramming of sheep fibroblasts into pluripotency under a drug-inducible expression of mouse-derived defined factors. PLoS One,2011,6:e15947.
[7]Liu J, Balehosur D, Murray B, Kelly JM, Sumer H, Verma PJ. Generation and characterization of reprogrammed sheep induced pluripotent stem cells. Theriogenology,2012,77:338-346 e331.
[8]Deng Y, Liu Q, Luo C, Chen S, Li X, Wang C, Liu Z, Lei X, Zhang H, Sun H, Lu F, Jiang J, Shi D. Generation of induced pluripotent stem cells from buffalo (Bubalus bubalis) fetal fibroblasts with buffalo defined factors. Stem Cells Dev,2012,21:2485-2494.
[9]Han X, Han J, Ding F, Cao S, Lim SS, Dai Y, Zhang R, Zhang Y, Lim B, Li N. Generation of induced pluripotent stem cells from bovine embryonic fibroblast cells. Cell Res,2011,21:1509-1512.
[10]Huang B, Li T, Alonso-Gonzalez L, Gorre R, Keatley S, Green A, Turner P, Kallingappa PK, Verma V, Oback B. A virus-free poly-promoter vector induces pluripotency in quiescent bovine cells under chemically defined conditions of dual kinase inhibition. PLoS One,2011,6:e24501.
[11]Esteban MA, Xu J, Yang J, Peng M, Qin D, Li W, Jiang Z, Chen J, Deng K, Zhong M, Cai J, Lai L, Pei D. Generation of induced pluripotent stem cell lines from Tibetan miniature pig. J Biol Chem, 2009,284:17634-17640.
[12]Ezashi T,Telugu BP,Alexenko AP, Sachdev S, Sinha S, Roberts RM. Derivation of induced pluripotent stem cells from pig somatic cells. Proc Natl Acad Sci USA,2009,106:10993-10998.
[13]Fan N, Chen J, Shang Z, Dou H, Ji G, Zou Q, Wu L, He L, Wang F, Liu K, Liu N, Han J, Zhou Q,Pan D,Yang D,Zhao B,Ouyang Z,Liu Z,Zhao Y,Lin L, Zhong C,Wang Q,Wang S,Xu Y, Luan J, Liang Y, Yang Z, Li J, Lu C, Vajta G, Li Z, Ouyang H, Wang H, Wang Y, Yang Y,Liu Z, Wei H, Luan Z, Esteban MA, Deng H, Yang H, Pei D, Li N, Pei G, Liu L, Du Y, Xiao L, Lai L. Piglets cloned from induced pluripotent stem cells. Cell Res,2013,23:162-166.
[14]Wu Z, Chen J, Ren J, Bao L, Liao J, Cui C, Rao L, Li H, Gu Y, Dai H, Zhu H, Teng X, Cheng L, Xiao L. Generation of pig induced pluripotent stem cells with a drug-inducible system. J Mol Cell Biol,2009,1:46-54.
[15]Liu K, Ji G, Mao J, Liu M, Wang L, Chen C, Liu L. Generation of Porcine-Induced Pluripotent Stem Cells by Using OCT4 and KLF4 Porcine Factors. Cell Reprogram,2012,14:505-513.
[16]Montserrat N, de Onate L, Garreta E, Gonzalez F, Adamo A, Eguizabal C, Hafner S, Vassena R, Izpisua Belmonte JC. Generation of feeder-free pig induced pluripotent stem cells without Pou5fl. Cell Transplant,2012,21:815-825.
[17]Kelly SJ. Studies of the developmental potential of 4-and 8-cell stage mouse blastomeres. J Exp Zool,1977,200:365-376.
[18]Yamanaka S, Blau HM. Nuclear reprogramming to a pluripotent state by three approaches. Nature, 2010,465:704-712.
[19]Yamanaka S. Strategies and new developments in the generation of patient-specific pluripotent stem cells. Cell Stem Cell,2007,1:39-49.
[20]Briggs R, King TJ. Transplantation of Living Nuclei From Blastula Cells into Enucleated Frogs' Eggs. Proc Natl Acad Sci USA,1952,38:455-463.
[21]Gurdon JB, Byrne JA. The first half-century of nuclear transplantation. Proc Natl Acad Sci USA, 2003,100:8048-8052.
[22]Bromhall JD. Nuclear transplantation in the rabbit egg. Nature,1975,258:719-722.
[23]Wilmut I, Schnieke AE, McWhir J, Kind AJ, Campbell KH. Viable offspring derived from fetal and adult mammalian cells. Cloning Stem Cells,2007,9:3-7.
[24]Hochedlinger K, Jaenisch R. Monoclonal mice generated by nuclear transfer from mature B and T donor cells. Nature,2002,415:1035-1038.
[25]Blelloch R, Wang Z, Meissner A, Pollard S, Smith A, Jaenisch R. Reprogramming efficiency following somatic cell nuclear transfer is influenced by the differentiation and methylation state of the donor nucleus. Stem Cells,2006,24:2007-2013.
[26]Wakayama T, Tabar V, Rodriguez I, Perry AC, Studer L, Mombaerts P. Differentiation of embryonic stem cell lines generated from adult somatic cells by nuclear transfer. Science,2001,292:740-743.
[27]Hochedlinger K, Jaenisch R. Nuclear transplantation, embryonic stem cells, and the potential for cell therapy. N Engl J Med,2003,349:275-286.
[28]Hwang WS, Ryu YJ, Park JH, Park ES, Lee EG, Koo JM, Jeon HY, Lee BC, Kang SK, Kim SJ, Ahn C, Hwang JH, Park KY, Cibelli JB,Moon SY. Evidence of a pluripotent human embryonic stem cell line derived from a cloned blastocyst. Science,2004,303:1669-1674.
[29]Hwang WS, Roh SI, Lee BC, Kang SK, Kwon DK, Kim S, Kim SJ, Park SW, Kwon HS, Lee CK, Lee JB, Kim JM, Ahn C, Paek SH, Chang SS, Koo JJ, Yoon HS, Hwang JH, Hwang YY, Park YS, Oh SK, Kim HS, Park JH, Moon SY, Schatten G Patient-specific embryonic stem cells derived from human SCNT blastocysts. Science,2005,308:1777-1783.
[30]Egli D, Rosains J, Birkhoff G, Eggan K. Developmental reprogramming after chromosome transfer into mitotic mouse zygotes. Nature,2007,447:679-685.
[31]Kikyo N, Wade PA, Guschin D, Ge H, Wolffe AP. Active remodeling of somatic nuclei in egg cytoplasm by the nucleosomal ATPase ISWI. Science,2000,289:2360-2362.
[32]Hansis C, Barreto G, Maltry N, Niehrs C. Nuclear reprogramming of human somatic cells by xenopus egg extract requires BRG1. Curr Biol,2004,14:1475-1480.
[33]Gonda K, Fowler J, Katoku-Kikyo N, Haroldson J, Wudel J, Kikyo N. Reversible disassembly of somatic nucleoli by the germ cell proteins FRGY2a and FRGY2b. Nat Cell Biol,2003,5:205-210.
[34]Tamada H, Van Thuan N, Reed P, Nelson D, Katoku-Kikyo N, Wudel J, Wakayama T, Kikyo N. Chromatin decondensation and nuclear reprogramming by nucleoplasmin. Mol Cell Biol,2006,26: 1259-1271.
[35]Miller RA, Ruddle FH. Pluripotent teratocarcinoma-thymus somatic cell hybrids. Cell,1976,9: 45-55.
[36]Tada M, Takahama Y, Abe K, Nakatsuji N, Tada T. Nuclear reprogramming of somatic cells by in vitro hybridization with ES cells. Curr Biol,2001,11:1553-1558.
[37]Cowan CA, Atienza J, Melton DA, Eggan K. Nuclear reprogramming of somatic cells after fusion with human embryonic stem cells. Science,2005,309:1369-1373.
[38]Yu J, Vodyanik MA, He P, Slukvin, II, Thomson JA. Human embryonic stem cells reprogram myeloid precursors following cell-cell fusion. Stem Cells,2006,24:168-176.
[39]Kimura H, Tada M, Nakatsuji N, Tada T. Histone code modifications on pluripotential nuclei of reprogrammed somatic cells. Mol Cell Biol,2004,24:5710-5720.
[40]Matsumura H, Tada M, Otsuji T, Yasuchika K, Nakatsuji N, Surani A, Tada T. Targeted chromosome elimination from ES-somatic hybrid cells. Nat Methods,2007,4:23-25.
[41]Chambers I, Colby D, Robertson M, Nichols J, Lee S, Tweedie S, Smith A. Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells. Cell,2003,113: 643-655.
[42]Mitsui K, Tokuzawa Y, Itoh H, Segawa K, Murakami M, Takahashi K, Maruyama M, Maeda M, Yamanaka S. The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells. Cell,2003,113:631-642.
[43]Taranger CK, Noer A, Sorensen AL, Hakelien AM, Boquest AC, Collas P. Induction of dedifferentiation, genomewide transcriptional programming, and epigenetic reprogramming by extracts of carcinoma and embryonic stem cells. Mol Biol Cell,2005,16:5719-5735.
[44]Do JT, Scholer HR. Nuclei of embryonic stem cells reprogram somatic cells. Stem Cells,2004,22: 941-949.
[45]Strelchenko N, Kukharenko V, Shkumatov A, Verlinsky O, Kuliev A, Verlinsky Y. Reprogramming of human somatic cells by embryonic stem cell cytoplast. Reprod Biomed Online,2006,12: 107-111.
[46]Silva J, Chambers I, Pollard S, Smith A. Nanog promotes transfer of pluripotency after cell fusion. Nature,2006,441:997-1001.
[47]Darr H, Mayshar Y, Benvenisty N. Overexpression of NANOG in human ES cells enables feeder-free growth while inducing primitive ectoderm features. Development,2006,133: 1193-1201.
[48]Hatano SY, Tada M, Kimura H, Yamaguchi S, Kono T, Nakano T, Suemori H, Nakatsuji N, Tada T. Pluripotential competence of cells associated with Nanog activity. Mech Dev,2005,122:67-79.
[49]Ivanova N, Dobrin R, Lu R, Kotenko I, Levorse J, DeCoste C, Schafer X, Lun Y, Lemischka IR. Dissecting self-renewal in stem cells with RNA interference. Nature,2006,442:533-538.
[50]Zaehres H, Lensch MW, Daheron L, Stewart SA, Itskovitz-Eldor J, Daley GQ. High-efficiency RNA interference in human embryonic stem cells. Stem Cells,2005,23:299-305.
[51]Matsui Y, Zsebo K, Hogan BL. Derivation of pluripotential embryonic stem cells from murine primordial germ cells in culture. Cell,1992,70:841-847.
[52]Jiang Y, Jahagirdar BN, Reinhardt RL, Schwartz RE, Keene CD, Ortiz-Gonzalez XR, Reyes M, Lenvik T, Lund T, Blackstad M, Du J, Aldrich S, Lisberg A, Low WC, Largaespada DA, Verfaillie CM. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature,2002,418:41-49.
[53]Kanatsu-Shinohara M, Inoue K, Lee J, Yoshimoto M, Ogonuki N, Miki H, Baba S, Kato T, Kazuki Y, Toyokuni S, Toyoshima M, Niwa O,Oshimura M, Heike T, Nakahata T, Ishino F, Ogura A, Shinohara T. Generation of pluripotent stem cells from neonatal mouse testis. Cell,2004,119: 1001-1012.
[54]Guan K, Nayernia K, Maier LS, Wagner S, Dressel R, Lee JH, Nolte J, Wolf F, Li M, Engel W, Hasenfuss G. Pluripotency of spermatogonial stem cells from adult mouse testis. Nature,2006, 440:1199-1203.
[55]Hernandez L, Kozlov S, Piras G, Stewart CL. Paternal and maternal genomes confer opposite effects on proliferation, cell-cycle length, senescence, and tumor formation. Proc Natl Acad Sci USA,2003,100:13344-13349.
[56]Allen ND, Barton SC, Hilton K, Norris ML, Surani MA. A functional analysis of imprinting in parthenogenetic embryonic stem cells. Development,1994,120:1473-1482.
[57]Cibelli JB, Grant KA, Chapman KB, Cunniff K, Worst T, Green HL, Walker SJ, Gutin PH, Vilner L, Tabar V, Dominko T, Kane J, Wettstein PJ, Lanza RP, Studer L, Vrana KE, West MD. Parthenogenetic stem cells in nonhuman primates. Science,2002,295:819.
[58]Kim K, Lerou P, Yabuuchi A, Lengerke C, Ng K, West J, Kirby A, Daly MJ, Daley GQ. Histocompatible embryonic stem cells by parthenogenesis. Science,2007,315:482-486.
[59]Maherali N, Sridharan R, Xie W, Utikal J, Eminli S, Arnold K, Stadtfeld M, Yachechko R, Tchieu J, Jaenisch R, Plath K, Hochedlinger K. Directly reprogrammed fibroblasts show global epigenetic remodeling and widespread tissue contribution. Cell Stem Cell,2007,1:55-70.
[60]Okita K, Ichisaka T, Yamanaka S. Generation of germline-competent induced pluripotent stem cells. Nature,2007,448:313-317.
[61]Wernig M, Meissner A, Foreman R, Brambrink T, Ku M, Hochedlinger K, Bernstein BE, Jaenisch R. In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature,2007,448: 318-324.
[62]Stadtfeld M, Nagaya M, Utikal J, Weir G, Hochedlinger K. Induced pluripotent stem cells generated without viral integration. Science,2008,322:945-949.
[63]Stadtfeld M, Maherali N, Breault DT, Hochedlinger K. Defining molecular cornerstones during fibroblast to iPS cell reprogramming in mouse. Cell Stem Cell,2008,2:230-240.
[64]Okita K, Nakagawa M, Hyenjong H, Ichisaka T, Yamanaka S. Generation of mouse induced pluripotent stem cells without viral vectors. Science,2008,322:949-953.
[65]Huangfu D, Maehr R, Guo W, Eijkelenboom A, Snitow M, Chen AE, Melton DA. Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds. Nat Biotechnol,2008,26:795-797.
[66]Aoi T, Yae K, Nakagawa M, Ichisaka T, Okita K, Takahashi K, Chiba T, Yamanaka S. Generation of pluripotent stem cells from adult mouse liver and stomach cells. Science,2008,321:699-702.
[67]Shi Y, Do JT, Desponts C, Hahm HS, Scholer HR, Ding S. A combined chemical and genetic approach for the generation of induced pluripotent stem cells. Cell Stem Cell,2008,2:525-528.
[68]Di Stefano B, Prigione A, Broccoli V. Efficient genetic reprogramming of unmodified somatic neural progenitors uncovers the essential requirement of Oct4 and Klf4. Stem Cells Dev,2009,18: 707-716.
[69]Takahashi K, Mitsui K, Yamanaka S. Role of ERas in promoting tumour-like properties in mouse embryonic stem cells. Nature,2003,423:541-545.
[70]Adhikary S, Eilers M. Transcriptional regulation and transformation by Myc proteins. Nat Rev Mol Cell Biol,2005,6:635-645.
[71]Rowland BD, Bernards R, Peeper DS. The KLF4 tumour suppressor is a transcriptional repressor of p53 that acts as a context-dependent oncogene. Nat Cell Biol,2005,7:1074-1082.
[72]Meshorer E, Yellajoshula D, George E, Scambler PJ, Brown DT, Misteli T. Hyperdynamic plasticity of chromatin proteins in pluripotent embryonic stem cells. Dev Cell,2006,10:105-116.
[73]Knoepfler PS, Zhang XY, Cheng PF, Gafken PR, McMahon SB, Eisenman RN. Myc influences global chromatin structure. EMBO J,2006,25:2723-2734.
[74]Nakatake Y, Fukui N, Iwamatsu Y, Masui S, Takahashi K, Yagi R, Yagi K, Miyazaki J, Matoba R, Ko MS, Niwa H. Klf4 cooperates with Oct3/4 and Sox2 to activate the Leftyl core promoter in embryonic stem cells. Mol Cell Biol,2006,26:7772-7782.
[75]Masui S, Nakatake Y, Toyooka Y, Shimosato D, Yagi R, Takahashi K, Okochi H, Okuda A, Matoba R, Sharov AA, Ko MS, Niwa H. Pluripotency governed by Sox2 via regulation of Oct3/4 expression in mouse embryonic stem cells. Nat Cell Biol,2007,9:625-635.
[76]Hochedlinger K, Yamada Y, Beard C, Jaenisch R. Ectopic expression of Oct-4 blocks progenitor-cell differentiation and causes dysplasia in epithelial tissues. Cell,2005,121:465-477.
[77]Boyer LA, Plath K, Zeitlinger J, Brambrink T, Medeiros LA, Lee TI, Levine SS, Wernig M, Tajonar A, Ray MK, Bell GW, Otte AP, Vidal M,Gifford DK, Young RA, Jaenisch R. Polycomb complexes repress developmental regulators in murine embryonic stem cells. Nature,2006,441:349-353.
[78]Niwa H, Miyazaki J, Smith AG. Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells. Nat Genet,2000,24:372-376.
[79]Zhou S, Ding C, Zhao X, Wang E, Dai X, Liu L, Li W, Liu Z, Wan H, Feng C, Hai T, Wang L, Zhou Q. Successful generation of cloned mice using nuclear transfer from induced pluripotent stem cells. Cell Res,2010,20:850-853.
[80]Kaji K, Norrby K, Paca A, Mileikovsky M, Mohseni P, Woltjen K. Virus-free induction of pluripotency and subsequent excision of reprogramming factors. Nature,2009,458:771-775.
[81]Woltjen K, Michael IP, Mohseni P, Desai R, Mileikovsky M, Hamalainen R, Cowling R, Wang W, Liu P, Gertsenstein M, Kaji K, Sung HK, Nagy A. piggyBac transposition reprograms fibroblasts to induced pluripotent stem cells. Nature,2009,458:766-770.
[82]Yu J, Hu K, Smuga-Otto K, Tian S, Stewart R, Slukvin Ⅱ, Thomson JA. Human induced pluripotent stem cells free of vector and transgene sequences. Science,2009,324:797-801.
[83]Huangfu D, Osafune K, Maehr R, Guo W, Eijkelenboom A, Chen S, Muhlestein W, Melton DA. Induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2. Nat Biotechnol,2008,26:1269-1275.
[84]Marson A, Levine SS, Cole MF, Frampton GM, Brambrink T, Johnstone S, Guenther MG, Johnston WK, Wernig M, Newman J,Calabrese JM, Dennis LM, Volkert TL, Gupta S, Love J, Hannett N, Sharp PA, Bartel DP, Jaenisch R, Young RA. Connecting microRNA genes to the core transcriptional regulatory circuitry of embryonic stem cells. Cell,2008,134:521-533.
[85]Shi Y, Desponts C, Do JT, Hahm HS, Scholer HR, Ding S. Induction of pluripotent stem cells from mouse embryonic fibroblasts by Oct4 and Klf4 with small-molecule compounds. Cell Stem Cell, 2008,3:568-574.
[86]Meissner A, Wernig M, Jaenisch R. Direct reprogramming of genetically unmodified fibroblasts into pluripotent stem cells. Nat Biotechnol,2007,25:1177-1181.
[87]Okamoto K, Okazawa H, Okuda A, Sakai M, Muramatsu M, Hamada H. A novel octamer binding transcription factor is differentially expressed in mouse embryonic cells. Cell,1990,60:461-472.
[88]Rosner MH, Vigano MA, Ozato K, Timmons PM, Poirier F, Rigby PW, Staudt LM. A POU-domain transcription factor in early stem cells and germ cells of the mammalian embryo. Nature,1990,345: 686-692.
[89]Scholer HR, Ruppert S, Suzuki N, Chowdhury K, Gruss P. New type of POU domain in germ line-specific protein Oct-4. Nature,1990,344:435-439.
[90]Nichols J, Zevnik B, Anastassiadis K, Niwa H, Klewe-Nebenius D, Chambers I, Scholer H, Smith A. Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4. Cell,1998,95:379-391.
[91]Shimozaki K, Nakashima K, Niwa H, Taga T. Involvement of Oct3/4 in the enhancement of neuronal differentiation of ES cells in neurogenesis-inducing cultures. Development,2003,130: 2505-2512.
[92]Zeineddine D, Papadimou E, Chebli K, Gineste M, Liu J, Grey C, Thurig S, Behfar A, Wallace VA, Skerjanc IS, Puceat M. Oct-3/4 dose dependently regulates specification of embryonic stem cells toward a cardiac lineage and early heart development. Dev Cell,2006,11:535-546.
[93]Yuan H, Corbi N, Basilico C, Dailey L. Developmental-specific activity of the FGF-4 enhancer requires the synergistic action of Sox2 and Oct-3. Genes Dev,1995,9:2635-2645.
[94]Avilion AA, Nicolis SK, Pevny LH, Perez L, Vivian N, Lovell-Badge R. Multipotent cell lineages in early mouse development depend on SOX2 function. Genes Dev,2003,17:126-140.
[95]Li M, Pevny L, Lovell-Badge R, Smith A. Generation of purified neural precursors from embryonic stem cells by lineage selection. Curr Biol,1998,8:971-974.
[96]Zappone MV, Galli R, Catena R,Meani N, De Biasi S,Mattei E,Tiveron C, Vescovi AL, Lovell-Badge R, Ottolenghi S, Nicolis SK. Sox2 regulatory sequences direct expression of a (beta)-geo transgene to telencephalic neural stem cells and precursors of the mouse embryo, revealing regionalization of gene expression in CNS stem cells. Development,2000,127: 2367-2382.
[97]Kamachi Y, Uchikawa M, Kondoh H. Pairing SOX off:with partners in the regulation of embryonic development. Trends Genet,2000,16:182-187.
[98]Wilson M, Koopman P, Matching SOX:partner proteins and co-factors of the SOX family of transcriptional regulators. Curr Opin Genet Dev,2002,12:441-446.
[99]Nishimoto M, Miyagi S, Katayanagi T, Tomioka M, Muramatsu M, Okuda A. The embryonic Octamer factor 3/4 displays distinct DNA binding specificity from those of other Octamer factors. Biochem Biophys Res Commun,2003,302:581-586.
[100]Tokuzawa Y, Kaiho E, Marayama M, Takahashi K, Mitsui K, Maeda M, Niwa H, Yamanaka S. Fbx15 is a novel target of Oct3/4 but is dispensable for embryonic stem cell self-renewal and mouse development. Mol Cell Biol,2003,23:2699-2708.
[101]Chew JL, Loh YH, Zhang W, Chen X, Tam WL, Yeap LS, Li P, Ang YS, Lim B, Robson P, Ng HH. Reciprocal transcriptional regulation of Pou5fl and Sox2 via the Oct4/Sox2 complex in embryonic stem cells. Mol Cell Biol,2005,25:6031-6046.
[102]Okumura-Nakanishi S, Saito M, Niwa H, Ishikawa F. Oct-3/4 and Sox2 regulate Oct-3/4 gene in embryonic stem cells. J Biol Chem,2005,280:5307-5317.
[103]Tomioka M, Nishimoto M, Miyagi S, Katayanagi T, Fukui N, Niwa H, Muramatsu M, Okuda A. Identification of Sox-2 regulatory region which is under the control of Oct-3/4-Sox-2 complex. Nucleic Acids Res,2002,30:3202-3213.
[104]Kuroda T, Tada M, Kubota H, Kimura H, Hatano SY, Suemori H, Nakatsuji N, Tada T. Octamer and Sox elements are required for transcriptional cis regulation of Nanog gene expression. Mol Cell Biol,2005,25:2475-2485.
[105]Rodda DJ, Chew JL, Lim LH, Loh YH, Wang B, Ng HH, Robson P. Transcriptional regulation of nanog by OCT4 and SOX2. J Biol Chem,2005,280:24731-24737.
[106]Boyer LA, Lee TI, Cole MF, Johnstone SE, Levine SS, Zucker JP, Guenther MG, Kumar RM, Murray HL, Jenner RG, Gifford DK, Melton DA, Jaenisch R, Young RA. Core transcriptional regulatory circuitry in human embryonic stem cells. Cell,2005,122:947-956.
[107]Loh YH, Wu Q, Chew JL, Vega VB, Zhang W, Chen X, Bourque G, George J, Leong B, Liu J, Wong KY, Sung KW, Lee CW, Zhao XD,Chiu KP, Lipovich L, Kuznetsov VA, Robson P, Stanton LW, Wei CL, Ruan Y, Lim B, Ng HH. The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells. Nat Genet,2006,38:431-440.
[108]Dalla-Favera R, Bregni M, Erikson J, Patterson D, Gallo RC, Croce CM. Human c-myc one gene is located on the region of chromosome 8 that is translocated in Burkitt lymphoma cells. Proc Natl Acad Sci USA,1982,79:7824-7827.
[109]Davis AC, Wims M, Spotts GD, Hann SR, Bradley A. A null c-myc mutation causes lethality before 10.5 days of gestation in homozygotes and reduced fertility in heterozygous female mice. Genes Dev,1993,7:671-682.
[110]Baudino TA, McKay C, Pendeville-Samain H, Nilsson JA, Maclean KH, White EL, Davis AC, Ihle JN, Cleveland JL. c-Myc is essential for vasculogenesis and angiogenesis during development and tumor progression. Genes Dev,2002,16:2530-2543.
[111]Cartwright P, McLean C, Sheppard A, Rivett D, Jones K, Dalton S. LIF/STAT3 controls ES cell self-renewal and pluripotency by a Myc-dependent mechanism. Development,2005,132: 885-896.
[112]Cawley S, Bekiranov S, Ng HH, Kapranov P, Sekinger EA, Kampa D, Piccolboni A, Sementchenko V, Cheng J, Williams AJ, Wheeler R, Wong B, Drenkow J, Yamanaka M, Patel S, Brubaker S, Tammana H, Helt G, Struhl K, Gingeras TR. Unbiased mapping of transcription factor binding sites along human chromosomes 21 and 22 points to widespread regulation of noncoding RNAs. Cell,2004,116:499-509.
[113]Fernandez PC, Frank SR, Wang L, Schroeder M, Liu S, Greene J, Cocito A, Amati B. Genomic targets of the human c-Myc protein. Genes Dev,2003,17:1115-1129.
[114]Li Z, Van Calcar S, Qu C, Cavenee WK, Zhang MQ, Ren B. A global transcriptional regulatory role for c-Myc in Burkitt's lymphoma cells. Proc Natl Acad Sci USA,2003,100:8164-8169.
[115]Grandori C, Wu KJ, Fernandez P, Ngouenet C, Grim J, Clurman BE, Moser MJ, Oshima J, Russell DW, Swisshelm K, Frank S, Amati B,Dalla-Favera R, Monnat RJ Jr. Werner syndrome protein limits MYC-induced cellular senescence. Genes Dev,2003,17:1569-1574.
[116]Peukert K, Staller P, Schneider A, Carmichael G, Hanel F, Eilers M. An alternative pathway for gene regulation by Myc. EMBO J,1997,16:5672-5686.
[117]O'Donnell KA, Wentzel EA, Zeller KI, Dang CV, Mendell JT. c-Myc-regulated microRNAs modulate E2F1 expression. Nature,2005,435:839-843.
[118]Schuh R, Aicher W, Gaul U, Cote S, Preiss A, Maier D, Seifert E, Nauber U, Schroder C, Kemler R. A conserved family of nuclear proteins containing structural elements of the finger protein encoded by Kruppel, a Drosophila segmentation gene. Cell,1986,47:1025-1032.
[119]Garrett-Sinha LA, Eberspaecher H, Seldin MF, de Crombrugghe B. A gene for a novel zinc-finger protein expressed in differentiated epithelial cells and transiently in certain mesenchymal cells. J Biol Chem,1996,271:31384-31390.
[120]Shields JM, Christy RJ, Yang VW. Identification and characterization of a gene encoding a gut-enriched Kruppel-like factor expressed during growth arrest. J Biol Chem,1996,271: 20009-20017.
[121]Chen X, Johns DC, Geiman DE, Marban E, Dang DT, Hamlin G, Sun R, Yang VW. Kruppel-like factor 4 (gut-enriched Kruppel-like factor) inhibits cell proliferation by blocking G1/S progression of the cell cycle. J Biol Chem,2001,276:30423-30428.
[122]Segre JA, Bauer C, Fuchs E. K1f4 is a transcription factor required for establishing the barrier function of the skin. Nat Genet,1999,22:356-360.
[123]Katz JP, Perreault N, Goldstein BG, Lee CS, Labosky PA, Yang VW, Kaestner KH. The zinc-finger transcription factor Klf4 is required for terminal differentiation of goblet cells in the colon. Development,2002,129:2619-2628.
[124]Katz JP, Perreault N, Goldstein BG, Actman L, McNally SR, Silberg DG, Furth EE, Kaestner KH. Loss of Klf4 in mice causes altered proliferation and differentiation and precancerous changes in the adult stomach. Gastroenterology,2005,128:935-945.
[125]Foster KW, Frost AR, McKie-Bell P, Lin CY, Engler JA, Grizzle WE, Ruppert JM. Increase of GKLF messenger RNA and protein expression during progression of breast cancer. Cancer Res, 2000,60:6488-6495.
[126]Foster KW, Ren S, Louro ID, Lobo-Ruppert SM, McKie-Bell P, Grizzle W, Hayes MR, Broker TR, Chow LT, Ruppert JM. Oncogene expression cloning by retroviral transduction of adenovirus E1A-immortalized rat kidney RK3E cells:transformation of a host with epithelial features by c-MYC and the zinc finger protein GKLF. Cell Growth Differ,1999,10:423-434.
[127]Foster KW, Liu Z, Nail CD, Li X, Fitzgerald TJ, Bailey SK, Frost AR, Louro ID, Townes TM, Paterson AJ, Kudlow JE, Lobo-Ruppert SM,Ruppert JM. Induction of KLF4 in basal keratinocytes blocks the proliferation-differentiation switch and initiates squamous epithelial dysplasia. Oncogene,2005,24:1491-1500.
[128]Rowland BD, Peeper DS. KLF4, p21 and context-dependent opposing forces in cancer. Nat Rev Cancer,2006,6:11-23.
[129]Li Y, McClintick J, Zhong L, Edenberg HJ, Yoder MC, Chan RJ. Murine embryonic stem cell differentiation is promoted by SOCS-3 and inhibited by the zinc finger transcription factor K1f4. Blood,2005,105:635-637.
[130]Loh YH, Ng JH, Ng HH. Molecular framework underlying pluripotency. Cell Cycle,2008,7: 885-891.
[131]Amabile G, Meissner A. Induced pluripotent stem cells:current progress and potential for regenerative medicine. Trends Mol Med,2009,15:59-68.
[132]Viswanathan SR, Daley GQ, Gregory RI. Selective blockade of microRNA processing by Lin28. Science,2008,320:97-100.
[133]Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM. Embryonic stem cell lines derived from human blastocysts. Science,1998,282:1145-1147.
[134]Hanna J, Wernig M, Markoulaki S, Sun CW, Meissner A, Cassady JP, Beard C, Brambrink T, Wu LC, Townes TM, Jaenisch R. Treatment of sickle cell anemia mouse model with iPS cells generated from autologous skin. Science,2007,318:1920-1923.
[135]Saporta MA. Grskovic M, Dimos JT. Induced pluripotent stem cells in the study of neurological diseases. Stem Cell Res Ther,2011,5:37.
[136]Mauritz C, Schwanke K, Reppel M, Neef S, Katsirntaki K, Maier LS, Nguemo F, Menke S, Haustein M, Hescheler J, Hasenfuss G, Martin U. Generation of functional murine cardiac myocytes from induced pluripotent stem cells. Circulation,2008,118:507-517.
[137]Narazaki G, Uosaki H, Teranishi M, Okita K, Kim B, Matsuoka S, Yamanaka S, Yamashita JK. Directed and systematic differentiation of cardiovascular cells from mouse induced pluripotent stem cells. Circulation,2008,118:498-506.
[138]Chamberlain SJ, Li XJ, Lalande M. Induced pluripotent stem (iPS) cells as in vitro models of human neurogenetic disorders. Neurogenetics,2008,9:227-235.
[139]Xu D, Alipio Z, Fink LM, Adcock DM, Yang J, Ward DC, Ma Y. Phenotypic correction of murine hemophilia A using an iPS cell-based therapy. Proc Natl Acad Sci USA,2009,106:808-813.
[140]Nakagawa M, Koyanagi M, Tanabe K, Takahashi K, Ichisaka T, Aoi T, Okita K, Mochiduki Y, Takizawa N, Yamanaka S. Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nat Biotechnol,200826:101-106.
[141]Gurdon J, Murdoch A. Nuclear transfer and iPS may work best together. Cell Stem Cell,2008,2: 135-138.
[142]Brambrink T, Foreman R, Welstead GG, Lengner CJ, Wernig M, Suh H, Jaenisch R. Sequential expression of pluripotency markers during direct reprogramming of mouse somatic cells. Cell Stem Cell,2008,2:151-159.
[143]McCormack MP, Rabbitts TH. Activation of the T-cell oncogene LMO2 after gene therapy for X-linked severe combined immunodeficiency. N Engl J Med,2004,350:913-922.
[144]Raper SE, Chirmule N, Lee FS, Wivel NA, Bagg A, Gao GP, Wilson JM, Batshaw ML. Fatal systemic inflammatory response syndrome in a ornithine transcarbamylase deficient patient following adenoviral gene transfer. Mol Genet Metab,2003,80:148-158.
[145]Hacein-Bey-Abina S,Le Deist F, Carlier F, Bouneaud C,Hue C,De Villartay JP, Thrasher AJ, Wulffraat N, Sorensen R, Dupuis-Girod S,Fischer A, Davies EG, Kuis W, Leiva L, Cavazzana-Calvo M. Sustained correction of X-linked severe combined immunodeficiency by ex vivo gene therapy. N Engl J Med,2002,346:1185-1193.
[146]Hacein-Bey-Abina S, von Kalle C, Schmidt M, Le Deist F, Wulffraat N, McIntyre E, Radford I, Villeval JL, Fraser CC, Cavazzana-Calvo M,Fischer A. A serious adverse event after successful gene therapy for X-linked severe combined immunodeficiency. N Engl J Med,2003,348: 255-256.
[147]Rideout WM,3rd, Hochedlinger K, Kyba M, Daley GQ, Jaenisch R. Correction of a genetic defect by nuclear transplantation and combined cell and gene therapy. Cell,2002,109:17-27.
[148]Narayan AD, Chase JL, Lewis RL, Tian X, Kaufman DS, Thomson JA, Zanjani ED. Human embryonic stem cell-derived hematopoietic cells are capable of engrafting primary as well as secondary fetal sheep recipients. Blood,2006,107:2180-2183.
[149]Takagi Y, Takahashi J, Saiki H, Morizane A, Hayashi T, Kishi Y, Fukuda H, Okamoto Y, Koyanagi M, Ideguchi M, Hayashi H, Imazato T,Kawasaki H, Suemori H, Omachi S, Iida H, Itoh N, Nakatsuji N, Sasai Y, Hashimoto N. Dopaminergic neurons generated from monkey embryonic stem cells function in a Parkinson primate model. J Clin Invest,2005,115:102-109.
[150]Ishii T, Yasuchika K, Machimoto T, Kamo N, Komori J, Konishi S, Suemori H, Nakatsuji N, Saito M, Kohno K, Uemoto S, Ikai I. Transplantation of embryonic stem cell-derived endodermal cells into mice with induced lethal liver damage. Stem Cells,2007,25:3252-3260.
[151]Leor J, Gerecht S, Cohen S, Miller L, Holbova R, Ziskind A, Shachar M, Feinberg MS, Guetta E, Itskovitz-Eldor J. Human embryonic stem cell transplantation to repair the infarcted myocardium. Heart,2007,93:1278-1284.
[152]Boyd AS, Wu DC, Higashi Y, Wood KJ. A comparison of protocols used to generate insulin-producing cell clusters from mouse embryonic stem cells. Stem Cells,2008,26: 1128-1137.
[153]Evans MJ, Kaufman MH. Establishment in culture of pluripotential cells from mouse embryos. Nature,1981,292:154-156.
[154]Alberio R, Croxall N, Allegrucci C. Pig epiblast stem cells depend on activin/nodal signaling for pluripotency and self-renewal. Stem Cells Dev,2010,19:1627-1636.
[155]West FD, Terlouw SL, Kwon DJ, Mumaw JL, Dhara SK, Hasneen K, Dobrinsky JR, Stice SL. Porcine induced pluripotent stem cells produce chimeric offspring. Stem Cells Dev,2010,19: 1211-1220.
[156]West FD, Uhl EW, Liu Y, Stowe H, Lu Y, Yu P, Gallegos-Cardenas A, Pratt SL, Stice SL. Brief report:chimeric pigs produced from induced pluripotent stem cells demonstrate germline transmission and no evidence of tumor formation in young pigs. Stem Cells,2011,29:1640-1643.
[157]Zhou L, Wang W, Liu Y, Fernandez de Castro J, Ezashi T, Telugu BP, Roberts RM, Kaplan HJ, Dean DC. Differentiation of induced pluripotent stem cells of swine into rod photoreceptors and their integration into the retina. Stem Cells,2011,29:972-980.
[158]Telugu BP, Ezashi T, Roberts RM. Porcine induced pluripotent stem cells analogous to naive and primed embryonic stem cells of the mouse. Int J Dev Biol,2010,54:1703-1713.
[159]Sumer H, Liu J, Malaver-Ortega LF, Lim ML, Khodadadi K, Verma PJ. NANOG is a key factor for induction of pluripotency in bovine adult fibroblasts. J Anim Sci,2011,89:2708-2716.
[160]Sartori C, DiDomenico A I, Thomson AJ, Milne E, Lillico SG, Burdon TG, Whitelaw CB. Ovine-induced pluripotent stem cells can contribute to chimeric lambs. Cell Reprogram,2012,14: 8-19.
[161]Keefer CL, Pant D, Blomberg L, Talbot NC. Challenges and prospects for the establishment of embryonic stem cell lines of domesticated ungulates. Anim Reprod Sci,2007,98:147-168.
[162]Piedrahita J A, Moore K, Lee C, Oetama B, Weaks R, Ramsoondar J, Thomson J, Vasquez J. Advances in the generation of transgenic pigs via embryo-derived and primordial germ cell-derived cells. J Reprod Fertil Suppl,1997,52:245-254.
[163]Shim H, Gutierrez-Adan A, Chen LR, BonDurant RH, Behboodi E, Anderson GB. Isolation of pluripotent stem cells from cultured porcine primordial germ cells. Biol Reprod,1997,57: 1089-1095.
[164]Mueller S, Prelle K, Rieger N, Petznek H, Lassnig C, Luksch U,Aigner B, Baetscher M, Wolf E, Mueller M, Brem G. Chimeric pigs following blastocyst injection of transgenic porcine primordial germ cells. Mol Reprod Dev,1999,54:244-254.
[165]Tsung HC, Du ZW, Rui R, Li XL, Bao LP, Wu J, Bao SM, Yao Z. The culture and establishment of embryonic germ (EG) cell lines from Chinese mini swine. Cell Res,2003,13:195-202.
[166]Rui R, Shim H, Moyer AL, Anderson DL, Penedo CT, Rowe JD, BonDurant RH, Anderson GB. Attempts to enhance production of porcine chimeras from embryonic germ cells and preimplantation embryos. Theriogenology,2004,61:1225-1235.
[167]Kastenberg ZJ, Odorico JS. Alternative sources of pluripotency:science, ethics, and stem cells. Transplant Rev (Orlando),2008,22:215-222.
[168]Lu HE,Tsai MS, Yang YC,Yuan CC, Wang TH, Lin XZ, Tseng CP, Hwang SM. Selection of alkaline phosphatase-positive induced pluripotent stem cells from human amniotic fluid-derived cells by feeder-free system. Exp Cell Res,2011,317:1895-1903.
[169]Notarianni E, Galli C, Laurie S, Moor RM, Evans MJ. Derivation of pluripotent, embryonic cell lines from the pig and sheep. J Reprod Fertil Suppl,1991,43:255-260.
[170]Kirchhof N, Carnwath JW, Lemme E, Anastassiadis K, Scholer H, Niemann H. Expression pattern of Oct-4 in preimplantation embryos of different species. Biol Reprod,2000,63:1698-1705.
[171]Vejlsted M, Avery B, Schmidt M, Greve T, Alexopoulos N, Maddox-Hyttel P. Ultrastructural and immunohistochemical characterization of the bovine epiblast. Biol Reprod,2005,72:678-686.
[172]Rodriguez A, De Frutos C, Diez C, Caamano JN, Facal N, Duque P, Garcia-Ochoa C, G6mez E. Effects of human versus mouse leukemia inhibitory factor on the in vitro development of bovine embryos. Theriogenology,2007,67:1092-1095.
[173]Eggenschwiler R, Cantz T. Induced pluripotent stem cells generated without viral integration. Hepatology,2009,49:1048-1049.
[174]Fusaki N, Ban H, Nishiyama A, Saeki K, Hasegawa M. Efficient induction of transgene-free human pluripotent stem cells using a vector based on Sendai virus, an RNA virus that does not integrate into the host genome. Proc Jpn Acad Ser B Phys Biol Sci,2009,85:348-362.
[175]Talbot NC, Blomberg Le A. The pursuit of ES cell lines of domesticated ungulates. Stem Cell Rev, 2008,4:235-254.
[176]Wan YJ, Zhang YL, Zhou ZR, Jia RX, Li M, Song H, Wang ZY, Wang LZ, Zhang GM, You JH, Wang F. Efficiency of donor cell preparation and recipient oocyte source for production of transgenic cloned dairy goats harboring human lactoferrin. Theriogenology,2012,78:583-592.
[177]Maherali N, Ahfeldt T, Rigamonti A, Utikal J, Cowan C, Hochedlinger K. A high-efficiency system for the generation and study of human induced pluripotent stem cells. Cell Stem Cell,2008, 3:340-345.
[178]Fan N, Chen J, Shang Z, Dou H, Ji G, Zou Q, Wu L, He L, Wang F, Liu K, Liu N, Han J, Zhou Q, Pan D, Yang D, Zhao B, Ouyang Z, Liu Z,Zhao Y, Lin L, Zhong C, Wang Q, Wang S, Xu Y, Luan J, Liang Y, Yang Z, Li J, Lu C, Vajta G, Li Z, Ouyang H, Wang H, Wang Y, Yang Y,Liu Z, Wei H, Luan Z, Esteban MA, Deng H, Yang H, Pei D, Li N, Pei G, Liu L, Du Y, Xiao L, Lai L. Piglets cloned from induced pluripotent stem cells. Cell Res,2013,23:162-166.
[179]Kou Z, Kang L, Yuan Y, Tao Y, Zhang Y, Wu T, He J, Wang J, Liu Z, Gao S. Mice cloned from induced pluripotent stem cells (iPSCs). Biol Reprod,2010,83:238-243.
[180]Wilmut I, Beaujean N, de Sousa PA, Dinnyes A, King TJ,Paterson LA, Wells DN, Young LE. Somatic cell nuclear transfer. Nature,2002,419:583-586.
[181]Rideout WM 3rd, Wakayama T, Wutz A, Eggan K, Jackson-Grusby L, Dausman J, Yanagimachi R, Jaenisch R. Generation of mice from wild-type and targeted ES cells by nuclear cloning. Nat Genet,2000,24:109-110.
[182]Keefer CL. Production of bioproducts through the use of transgenic animal models. Anim Reprod Sci,2004,82-83:5-12.
[183]Donovan DM, Kerr DE, Wall RJ. Engineering disease resistant cattle. Transgenic Res,2005,14: 563-567.
[184]Wall RJ, Powell AM, Paape MJ, Kerr DE, Bannerman DD, Pursel VG, Wells KD, Talbot N, Hawk HW. Genetically enhanced cows resist intramammary Staphylococcus aureus infection. Nat Biotechnol,2005,23:445-451.
[185]Bavister B. The role of animal studies in supporting human assisted reproductive technology. Reprod Fertil Dev,2004,16:719-728.
[186]Ohgane J, Wakayama T, Senda S, Yamazaki Y, Inoue K, Ogura A, Marh J, Tanaka S, Yanagimachi R, Shiota K. The Sall3 locus is an epigenetic hotspot of aberrant DNA methylation associated with placentomegaly of cloned mice. Genes Cells,2004,9:253-260.
[187]Kang YK, Koo DB, Park JS, Choi YH, Chung AS, Lee KK, Han YM. Aberrant methylation of donor genome in cloned bovine embryos. Nat Genet,2001,28:173-177.
[188]Santos F, Zakhartchenko V, Stojkovic M, Peters A, Jenuwein T, Wolf E, Reik W, Dean W. Epigenetic marking correlates with developmental potential in cloned bovine preimplantation embryos. Curr Biol,2003,13:1116-1121.
[189]Dean W, Santos F, Stojkovic M, Zakhartchenko V, Walter J, Wolf E, Reik W. Conservation of methylation reprogramming in mammalian development:aberrant reprogramming in cloned embryos. Proc Natl Acad Sci USA,2001,98:13734-13738.
[190]Kishigami S, Mizutani E, Ohta H, Hikichi T, Thuan NV, Wakayama S, Bui HT, Wakayama T. Significant improvement of mouse cloning technique by treatment with trichostatin A after somatic nuclear transfer. Biochem Biophys Res Commun,2006,340:183-189.
[191]Balasubramanian S, Babai N, Chaudhuri A, Qiu F, Bhattacharya S, Dave BJ, Parameswaran S, Carson SD, Thoreson WB, Sharp JG,Rao M, Ahmad I. Non cell-autonomous reprogramming of adult ocular progenitors:generation of pluripotent stem cells without exogenous transcription factors. Stem Cells,2009,27:3053-3062.
[192]Kim JB, Greber B, Arauzo-Bravo MJ, Meyer J, Park KI, Zaehres H, Scholer HR. Direct reprogramming of human neural stem cells by OCT4. Nature,2009461:649-643.
[193]Li W, Zhou H, Abujarour R, Zhu S, Young Joo J, Lin T, Hao E, Scholer HR, Hayek A, Ding S. Generation of human-induced pluripotent stem cells in the absence of exogenous Sox2. Stem Cells, 2009,27:2992-3000.
[194]Aasen T, Raya A, Barrero MJ, Garreta E, Consiglio A, Gonzalez F, Vassena R, Bilic J, Pekarik V, Tiscornia G, Edel M, Boue S, Izpisua Belmonte JC. Efficient and rapid generation of induced pluripotent stem cells from human keratinocytes. Nat Biotechnol,2008,26:1276-1284.
[195]Tan KY, Eminli S, Hettmer S, Hochedlinger K, Wagers AJ. Efficient generation of iPS cells from skeletal muscle stem cells. PLoS One,2011,6:e26406.
[196]Hiratsuka M, Uno N, Ueda K, Kurosaki H, Imaoka N, Kazuki K, Ueno E, Akakura Y, Katoh M, Osaki M, Kazuki Y, Nakagawa M, Yamanaka S, Oshimura M. Integration-free iPS cells engineered using human artificial chromosome vectors. PLoS One,2011,6:e25961.
[197]Kane NM, Nowrouzi A, Mukherjee S, Blundell MP, Greig JA, Lee WK, Houslay MD, Milligan G, Mountford JC, von Kalle C, Schmidt M,Thrasher AJ, Baker AH. Lentivirus-mediated reprogramming of somatic cells in the absence of transgenic transcription factors. Mol Ther,2010, 18:2139-2145.
[198]Ralston A, Rossant J. Genetic regulation of stem cell origins in the mouse embryo. Clin Genet, 2005,68:106-112.
[199]Beddington RS, Robertson EJ. An assessment of the developmental potential of embryonic stem cells in the midgestation mouse embryo. Development,1989,105:733-737.
[200]Yaseen MA, Wrenzycki C, Herrmann D, Carnwath JW, Niemann H. Changes in the relative abundance of mRNA transcripts for insulin-like growth factor (IGF-I and IGF-II) ligands and their receptors (IGF-IR/IGF-IIR) in preimplantation bovine embryos derived from different in vitro systems. Reproduction,2001,122:601-610.
[201]Pandey A, Singh N, Gupta SC, Rana JS, Gupta N. Relative expression of cell growth regulatory genes insulin-like growth factors (IGF-1 and IGF-2) and their receptors (IGF-1R and IGF-2R) in somatic cell nuclear transferred (SCNT) and in vitro fertilized (IVF) pre-implantation buffalo embryos. Cell Biol Int,2009,33:555-564.
[202]Kim S, Lee GS, Lee SH, Kim HS, Jeong YW, Kim JH, Kang SK, Lee BC, Hwang WS. Embryotropic effect of insulin-like growth factor (IGF)-I and its receptor on development of porcine preimplantation embryos produced by in vitro fertilization and somatic cell nuclear transfer. Mol Reprod Dev,2005,72:88-97.
[203]Kim S, Lee SH, Kim JH, Jeong YW, Hashem MA, Koo OJ, Park SM, Lee EG, Hossein MS, Kang SK, Lee BC, Hwang WS. Anti-apoptotic effect of insulin-like growth factor (IGF)-I and its receptor in porcine preimplantation embryos derived from in vitro fertilization and somatic cell nuclear transfer. Mol Reprod Dev,2006,73:1523-1530.
[204]Miyoshi K, Mori H, Mizobe Y, Akasaka E, Ozawa A, Yoshida M, Sato M. Valproic acid enhances in vitro development and Oct-3/4 expression of miniature pig somatic cell nuclear transfer embryos. Cell Reprogram,2010,12:67-74.
[205]Han DW, Song SJ, Uhum SJ, Do JT, Kim NH, Chung KS, Lee HT. Expression of IGF2 and IGF receptor mRNA in bovine nuclear transferred embryos. Zygote,2003,11:245-252.
[206]Schultz GA, Hogan A, Watson AJ, Smith RM, Heyner S. Insulin, insulin-like growth factors and glucose transporters:temporal patterns of gene expression in early murine and bovine embryos. Reprod Fertil Dev,1992,4:361-371.
[207]Watson AJ, Hogan A, Hahnel A, Wiemer KE, Schultz GA. Expression of growth factor ligand and receptor genes in the preimplantation bovine embryo. Mol Reprod Dev,1992,31:87-95.
[208]Doherty AS, Temeles GL, Schultz RM. Temporal pattern of IGF-I expression during mouse preimplantation embryogenesis. Mol Reprod Dev,1994,37:21-26.
[209]Yoshida Y, Miyamura M, Hamano S, Yoshida M. Expression of growth factor ligand and their receptor mRNAs in bovine ova during in vitro maturation and after fertilization in vitro. J Vet Med Sci,1998,60:549-554.
[210]Lonergan P, Gutierrez-Adan A, Pintado B, Fair T, Ward F, Fuente JD, Boland M. Relationship between time of first cleavage and the expression of IGF-I growth factor, its receptor, and two housekeeping genes in bovine two-cell embryos and blastocysts produced in vitro. Mol Reprod Dev,2000,57:146-152.
[211]Rappolee DA, Sturm KS, Behrendtsen O, Schultz GA, Pedersen RA, Werb Z. Insulin-like growth factor Ⅱ acts through an endogenous growth pathway regulated by imprinting in early mouse embryos. Genes Dev,1992,6:939-952.
[212]Zhang X, Kidder GM, Watson AJ, Schultz GA, Armstrong DT. Possible roles of insulin and insulin-like growth factors in rat preimplantation development:investigation of gene expression by reverse transcription-polymerase chain reaction. J Reprod Fertil,1994,100:375-380.
[213]Daliri M, Rao KB, Kaur G, Garg S, Patil S, Totey SM. Expression of growth factor ligand and receptor genes in preimplantation stage water buffalo (Bubalus bubalis) embryos and oviduct epithelial cells. J Reprod Fertil,1999,117:61-70.
[214]Lighten AD, Hardy K, Winston RM, Moore GE. Expression of mRNA for the insulin-like growth factors and their receptors in human preimplantation embryos. Mol Reprod Dev,1997,47: 134-139.