小鼠孤雌胚胎及孤雌胚胎干细胞中印记基因的表达
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摘要
小鼠孤雌胚胎体内发育最多不能超过10.5d,发育失败的主要原因是胚外组织发育缺陷和印记基因表达的异常。随着小鼠孤雌二倍体和单倍体胚胎干细胞的建系成功,不仅能作为研究印记基因的理想模型,还能够作为种子细胞应用于细胞治疗,拓宽了小鼠孤雌生殖的研究领域和再生医学应用范围。孤雌胚胎聚合作为一种简便易行的技术手段,能够显著提高孤雌胚胎干细胞的建系效率,还能促使异质胚胎间的印记基因相互补偿从而更加趋近于正常受精的胚胎干细胞。我们在文中主要阐释了小鼠孤雌胚胎、孤雌聚合胚胎、孤雌二倍体胚胎干细胞、孤雌单倍体胚胎、孤雌聚合胚胎干细胞中印记基因的表达。
The development of mice parthenogenetic embryos can not be beyond 10. 5days,because of the defect in extra-embryonic tissues and the abnormal expression of imprinting gene. Establishment of mice diploid or haploid parthenogenetic embryonic stem cells may be applied for searching novel imprinting genes and for cell therapy,which broaden the field of scientific research and regenerative medicine. Aggregation of parthenogenetic embryos as a convenient method not only can notably increase the efficiency of establishing parthenogenetic stem cells but also improve the expression level of imprinting genes. This improvement probably achieves through compensation of imprinting genes expression among different parthenogenetic embryos. In this paper we discuss the expression of imprinting genes in mice parthenogenetic embryos, aggregated parthenogenetic embryos, parthenogenetic haploid embryonic stem cells,parthenogenetic diploid embryonic stem cells and parthenogenetic embryonic stem cells derived from aggregated embryos.
The development of mice parthenogenetic embryos can not be beyond 10. 5days,because of the defect in extra-embryonic tissues and the abnormal expression of imprinting gene. Establishment of mice diploid or haploid parthenogenetic embryonic stem cells may be applied for searching novel imprinting genes and for cell therapy,which broaden the field of scientific research and regenerative medicine. Aggregation of parthenogenetic embryos as a convenient method not only can notably increase the efficiency of establishing parthenogenetic stem cells but also improve the expression level of imprinting genes. This improvement probably achieves through compensation of imprinting genes expression among different parthenogenetic embryos. In this paper we discuss the expression of imprinting genes in mice parthenogenetic embryos, aggregated parthenogenetic embryos, parthenogenetic haploid embryonic stem cells,parthenogenetic diploid embryonic stem cells and parthenogenetic embryonic stem cells derived from aggregated embryos.
引文
[1]Shuai L,Zhou Q.Haploid embryonic stem cells serve as a new tool for mammalian genetic study[J].Stem Cell Res Ther,2014,5(1):20.
[2]Shi L,Yang H,Li J.Haploid embryonic stem cells:an ideal tool for mammalian genetic analyses[J].Protein Cell,2012,3(11):806-810.
[3].Didie M,Christalla P,Rubart M,et al.Zimmermann,Parthenogenetic stem cells for tissue-engineered heart repair[J].J Clin Invest,2013,123(3):1285-1298.
[4]Fulka H,Hirose M,Inoue K,et a.Production of mouse embryonic stem cell lines from maturing oocytes by direct conversion of meiosis into mitosis[J].Stem Cells,2011,29(3):517-527.
[5]Daughtry B,Mitalipov S.Concise review:parthenote stem cells for regenerative medicine:genetic,epigenetic,and developmental features[J].Stem Cells Transl Med,2014,3(3):290-298.
[6]Wu Q,Kumagai T,Kawahara M,et al.Regulated expression of two sets of paternally imprinted genes is necessary for mouse parthenogenetic development to term[J].Reproduction,2006,131(3):481-488.
[7]Kono T,Sotomaru Y,Katsuzawa Y,et al.Mouse parthenogenetic embryos with monoallelic H19 expression can develop to day 17.5 of gestation[J].Dev Biol,2002,243(2):294-300.
[8]Kono T,Obata Y,Wu Q,et al.Birth of parthenogenetic mice that can develop to adulthood[J].Nature,2004,428(6985):860-864.
[9]Chen Z,Liu Z,Huang J,et al.Birth of parthenote mice directly from parthenogenetic embryonic stem cells[J].Stem Cells,2009,27(9):2136-2145.
[10]Eckardt S,Leu NA,Yanchik A,et al.Gene therapy by allele selection in a mouse model of beta-thalassemia[J].J Clin Invest,2011,121(2):623-627.
[11]Wang ZD,Xue Y,Shan ZY,et al.Generation of mouse parthenogenetic embryonic stem cells and preliminary study of the differentiation ability to motor neurons[J].Yi Chuan,2011,33(11):1231-1238.
[12]Yan X,Yang Y,Liu W,et al.Differentiation of neuron-like cells from mouse parthenogenetic embryonic stem cells[J].Neural Regen Res,2013.8(4):293-300.
[13]Espejel S,Eckardt S,Harbell J,et al.Brief report:Parthenogenetic embryonic stem cells are an effective cell source for therapeutic liver repopulation[J].Stem Cells,2014,32(7):1983-1988.
[14]Kwak M,Hong S,Yu SL,et al.Parthenogenetic embryonic stem cells with H19 siRNA-mediated knockdown as a potential resource for cell therapy[J].Int J Mol Med,2012,29(2):257-262.
[15]Wan H,He Z,Dong M,et al.Parthenogenetic haploid embryonic stem cells produce fertile mice[J].Cell Res,2013,23(11):1330-1333.
[16]Takahashi S,Lee J,Kohda T,et al.Induction of the G2/M transition stabilizes haploid embryonic stem cells[J].Development,2014,141(20):3842-3847.
[17]Hsieh YC,Intawicha P,Lee KH,et al.LIF and FGF cooperatively support stemness of rabbit embryonic stem cells derived from parthenogenetically activated embryos[J].Cell Reprogram,2011,13(3):241-255.
[18]Brevini TA,Pennarossa G,Attanasio L,et al.Culture conditions and signalling networks promoting the establishment of cell lines from parthenogenetic and biparental pig embryos[J].Stem Cell Rev,2010,6(3):484-495.
[19]Yang H,Liu Z,Ma Y,et al.Generation of haploid embryonic stem cells from Macaca fascicularis monkey parthenotes[J].Cell Res,2013,23(10):1187-1200.
[20]Li J,He J,Lin G,et al.Inducing human parthenogenetic embryonic stem cells into isletlike clusters[J].Mol Med Rep,2014,10(6):2882-2890.
[21]Gonzalez R,Garitaonandia I,Crain A,et al.Proof of concept studies exploring the safety and functional activity of human parthenogenetic-derived neural stem cells for the treatment of parkinson’s disease[J].Cell Transplant,2015,24(4):681\|690.
[22]Maatouk DM,Resnick JL.Continuing primordial germ cell differentiation in the mouse embryo is a cell-intrinsic program sensitive to DNA methylation[J].Dev Biol,2003,258(1):201-208.
[23]Mac Donald WA,Mann MR.Epigenetic regulation of genomic imprinting from germ line to preimplantation[J].Mol Reprod Dev,2014,81(2):126-140.
[24]Croteau S,Menezo Y.Methylation in fertilised and parthenogenetic preimplantation mouse embryos[J].Zygote,1994,2(1):47-52.
[25]Kelsey G,Feil R.New insights into establishment and maintenance of DNA methylation imprints in mammals[J].Philos Trans R Soc Lond B Biol Sci,2013,368(1609):20110336.
[26]Horii T,Kimura M,Morita S,et al.Loss of genomic imprinting in mouse parthenogenetic embryonic stem cells[J].Stem Cells,2008,26(1):79-88.
[27]Sotomaru Y,Kawase Y,Ueda T,et al.Disruption of imprinted expression of U2afbp-rs/U2af1-rs1 gene in mouse parthenogenetic fetuses[J].J Biol Chem,2001,276(28):26694-26698.
[28]Hackett JA,Surani MA.DNA methylation dynamics during the mammalian life cycle[J].Philos Trans R Soc Lond B Biol Sci,2013,368(1609):20110328.
[29]Gong SP,Kim H,Lee EJ,et al.Change in gene expression of mouse embryonic stem cells derived from parthenogenetic activation[J].Hum Reprod,2009,24(4):805-814.
[30]Liu L,Luo GZ,Yang W,et al.Activation of the imprinted Dlk1-Dio3 region correlates with pluripotency levels of mouse stem cells[J].J Biol Chem,2010,285(25):19483-19490.
[31]Li W,Zhao XY,Wan HF,et al.i PS cells generated without c-Myc have active Dlk1-Dio3 region and are capable of producing full-term mice through tetraploid complementation[J].Cell Res,2011,21(3):550-553.
[32]Zeng TB,He HJ,Han ZB,et al.DNA methylation dynamics of a maternally methylated DMR in the mouse Dlk1-Dio3 domain[J].FEBS Lett,2014,588(24):4665-4671.
[33]Kota SK,Lleres D,Bouschet T,et al.ICR noncoding RNA expression controls imprinting and DNA replication at the Dlk1-Dio3domain[J].Dev Cell,2014,31(1):19-33.
[34]Leeb M,Walker R,Mansfield B,et a.Germline potential of parthenogenetic haploid mouse embryonic stem cells[J].Development,2012,139(18):3301-3305.
[35]Hudson QJ,Kulinski TM,Huetter SP,et al.Genomic imprinting mechanisms in embryonic and extraembryonic mouse tissues[J].Heredity(Edinb),2010,105(1):45-56.
[36]Shan ZY,Wu YS,Shen XH,et al.Aggregation of pre-implantation embryos improves establishment of parthenogenetic stem cells and expression of imprinted genes[J].Dev Growth Differ,2012,54(4):481-488.
[2]Shi L,Yang H,Li J.Haploid embryonic stem cells:an ideal tool for mammalian genetic analyses[J].Protein Cell,2012,3(11):806-810.
[3].Didie M,Christalla P,Rubart M,et al.Zimmermann,Parthenogenetic stem cells for tissue-engineered heart repair[J].J Clin Invest,2013,123(3):1285-1298.
[4]Fulka H,Hirose M,Inoue K,et a.Production of mouse embryonic stem cell lines from maturing oocytes by direct conversion of meiosis into mitosis[J].Stem Cells,2011,29(3):517-527.
[5]Daughtry B,Mitalipov S.Concise review:parthenote stem cells for regenerative medicine:genetic,epigenetic,and developmental features[J].Stem Cells Transl Med,2014,3(3):290-298.
[6]Wu Q,Kumagai T,Kawahara M,et al.Regulated expression of two sets of paternally imprinted genes is necessary for mouse parthenogenetic development to term[J].Reproduction,2006,131(3):481-488.
[7]Kono T,Sotomaru Y,Katsuzawa Y,et al.Mouse parthenogenetic embryos with monoallelic H19 expression can develop to day 17.5 of gestation[J].Dev Biol,2002,243(2):294-300.
[8]Kono T,Obata Y,Wu Q,et al.Birth of parthenogenetic mice that can develop to adulthood[J].Nature,2004,428(6985):860-864.
[9]Chen Z,Liu Z,Huang J,et al.Birth of parthenote mice directly from parthenogenetic embryonic stem cells[J].Stem Cells,2009,27(9):2136-2145.
[10]Eckardt S,Leu NA,Yanchik A,et al.Gene therapy by allele selection in a mouse model of beta-thalassemia[J].J Clin Invest,2011,121(2):623-627.
[11]Wang ZD,Xue Y,Shan ZY,et al.Generation of mouse parthenogenetic embryonic stem cells and preliminary study of the differentiation ability to motor neurons[J].Yi Chuan,2011,33(11):1231-1238.
[12]Yan X,Yang Y,Liu W,et al.Differentiation of neuron-like cells from mouse parthenogenetic embryonic stem cells[J].Neural Regen Res,2013.8(4):293-300.
[13]Espejel S,Eckardt S,Harbell J,et al.Brief report:Parthenogenetic embryonic stem cells are an effective cell source for therapeutic liver repopulation[J].Stem Cells,2014,32(7):1983-1988.
[14]Kwak M,Hong S,Yu SL,et al.Parthenogenetic embryonic stem cells with H19 siRNA-mediated knockdown as a potential resource for cell therapy[J].Int J Mol Med,2012,29(2):257-262.
[15]Wan H,He Z,Dong M,et al.Parthenogenetic haploid embryonic stem cells produce fertile mice[J].Cell Res,2013,23(11):1330-1333.
[16]Takahashi S,Lee J,Kohda T,et al.Induction of the G2/M transition stabilizes haploid embryonic stem cells[J].Development,2014,141(20):3842-3847.
[17]Hsieh YC,Intawicha P,Lee KH,et al.LIF and FGF cooperatively support stemness of rabbit embryonic stem cells derived from parthenogenetically activated embryos[J].Cell Reprogram,2011,13(3):241-255.
[18]Brevini TA,Pennarossa G,Attanasio L,et al.Culture conditions and signalling networks promoting the establishment of cell lines from parthenogenetic and biparental pig embryos[J].Stem Cell Rev,2010,6(3):484-495.
[19]Yang H,Liu Z,Ma Y,et al.Generation of haploid embryonic stem cells from Macaca fascicularis monkey parthenotes[J].Cell Res,2013,23(10):1187-1200.
[20]Li J,He J,Lin G,et al.Inducing human parthenogenetic embryonic stem cells into isletlike clusters[J].Mol Med Rep,2014,10(6):2882-2890.
[21]Gonzalez R,Garitaonandia I,Crain A,et al.Proof of concept studies exploring the safety and functional activity of human parthenogenetic-derived neural stem cells for the treatment of parkinson’s disease[J].Cell Transplant,2015,24(4):681\|690.
[22]Maatouk DM,Resnick JL.Continuing primordial germ cell differentiation in the mouse embryo is a cell-intrinsic program sensitive to DNA methylation[J].Dev Biol,2003,258(1):201-208.
[23]Mac Donald WA,Mann MR.Epigenetic regulation of genomic imprinting from germ line to preimplantation[J].Mol Reprod Dev,2014,81(2):126-140.
[24]Croteau S,Menezo Y.Methylation in fertilised and parthenogenetic preimplantation mouse embryos[J].Zygote,1994,2(1):47-52.
[25]Kelsey G,Feil R.New insights into establishment and maintenance of DNA methylation imprints in mammals[J].Philos Trans R Soc Lond B Biol Sci,2013,368(1609):20110336.
[26]Horii T,Kimura M,Morita S,et al.Loss of genomic imprinting in mouse parthenogenetic embryonic stem cells[J].Stem Cells,2008,26(1):79-88.
[27]Sotomaru Y,Kawase Y,Ueda T,et al.Disruption of imprinted expression of U2afbp-rs/U2af1-rs1 gene in mouse parthenogenetic fetuses[J].J Biol Chem,2001,276(28):26694-26698.
[28]Hackett JA,Surani MA.DNA methylation dynamics during the mammalian life cycle[J].Philos Trans R Soc Lond B Biol Sci,2013,368(1609):20110328.
[29]Gong SP,Kim H,Lee EJ,et al.Change in gene expression of mouse embryonic stem cells derived from parthenogenetic activation[J].Hum Reprod,2009,24(4):805-814.
[30]Liu L,Luo GZ,Yang W,et al.Activation of the imprinted Dlk1-Dio3 region correlates with pluripotency levels of mouse stem cells[J].J Biol Chem,2010,285(25):19483-19490.
[31]Li W,Zhao XY,Wan HF,et al.i PS cells generated without c-Myc have active Dlk1-Dio3 region and are capable of producing full-term mice through tetraploid complementation[J].Cell Res,2011,21(3):550-553.
[32]Zeng TB,He HJ,Han ZB,et al.DNA methylation dynamics of a maternally methylated DMR in the mouse Dlk1-Dio3 domain[J].FEBS Lett,2014,588(24):4665-4671.
[33]Kota SK,Lleres D,Bouschet T,et al.ICR noncoding RNA expression controls imprinting and DNA replication at the Dlk1-Dio3domain[J].Dev Cell,2014,31(1):19-33.
[34]Leeb M,Walker R,Mansfield B,et a.Germline potential of parthenogenetic haploid mouse embryonic stem cells[J].Development,2012,139(18):3301-3305.
[35]Hudson QJ,Kulinski TM,Huetter SP,et al.Genomic imprinting mechanisms in embryonic and extraembryonic mouse tissues[J].Heredity(Edinb),2010,105(1):45-56.
[36]Shan ZY,Wu YS,Shen XH,et al.Aggregation of pre-implantation embryos improves establishment of parthenogenetic stem cells and expression of imprinted genes[J].Dev Growth Differ,2012,54(4):481-488.
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