Cdc42 Activity Regulates Hematopoietic Stem Cell Aging and Rejuvenation

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• 作者：Maria  ; Carolina Florian¹ ; Karin Dö ; rr¹ ; Anja Niebel¹ ; Deidre Daria¹ ; Hubert Schrezenmeier² ; Markus Rojewski² ; Marie-Dominique Filippi³ ; Anja Hasenberg⁴ ; Matthias Gunzer⁴ ; Karin Scharffetter-Kochanek¹ ; Yi Zheng³ ; Hartmut Geiger¹ ; ³ ; ^{hartmut.geiger@uni-ulm.de}
• 刊名：Cell Stem Cell
• 出版年：2012
• 期刊代码：P15_19345909
• 类别：bio
• 出版时间：4 May, 2012
• 卷：10
• 期：5
• 页码：520-530
• 文件大小：1742 K

摘要

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Summary

The decline in hematopoietic function seen during aging involves a progressive reduction in the immune response and an increased incidence of myeloid malignancy, and has been linked to aging of hematopoietic stem cells (HSCs). The molecular mechanisms underlying HSC aging remain unclear. Here we demonstrate that elevated activity of the small RhoGTPase Cdc42 in aged HSCs is causally linked to HSC aging and correlates with a loss of polarity in aged HSCs. Pharmacological inhibition of Cdc42 activity functionally rejuvenates aged HSCs, increases the percentage of polarized cells in an aged HSC population, and restores the level and spatial distribution of histone H4 lysine 16 acetylation to聽a status similar to that seen in young HSCs. Our聽data therefore suggest a mechanistic role for Cdc42 activity in HSC biology and epigenetic regulation, and identify Cdc42 activity as a pharmacological target for ameliorating stem cell aging.