4.4 Article

Aging of human hematopoietic stem cells is linked to changes in Cdc42 activity

期刊

HAEMATOLOGICA
卷 107, 期 2, 页码 393-402

出版社

FERRATA STORTI FOUNDATION
DOI: 10.3324/haematol.2020.269670

关键词

-

资金

  1. DFG [GRK1789]

向作者/读者索取更多资源

This study characterizes age-related phenotypes of human hematopoietic stem cells (HSC). It reveals increased frequencies of HSC, hematopoietic progenitor cells, and lineage negative cells in the elderly, as well as a decreased frequency of multi-lymphoid progenitors. The elevated activity of Cdc42 in aged HSC contributes to age-related changes and offers a potential target for attenuating aging in human HSC.
In this study, we characterize age-related phenotypes of human hematopoietic stem cells (HSC). We report increased frequencies of HSC, hematopoietic progenitor cells and lineage negative cells in the elderly but a decreased frequency of multi-lymphoid progenitors. Aged human HSC further exhibited a delay in initiating division ex vivo though without changes in their division kinetics. The activity of the small RhoGTPase Cdc42 was elevated in aged human hematopoietic cells and we identified a positive correlation between Cdc42 activity and the frequency of HSC upon aging. The frequency of human HSC polar for polarity proteins was, similar to the mouse, decreased upon aging, while inhibition of Cdc42 activity via the specific pharmacological inhibitor of Cdc42 activity, CASIN, resulted in re-polarization of aged human HSC with respect to Cdc42. Elevated activity of Cdc42 in aged HSC thus contributed to age-related changes in HSC. Xenotransplant, using NBSGW mice as recipients, showed elevated chimerism in recipients of aged compared to young HSC. Aged HSC treated with CASIN ex vivo displayed an engraftment profile similar to recipients of young HSC. Taken together, our work reveals strong evidence for a role of elevated Cdc42 activity in driving aging of human HSC, and similar to mice, this presents a likely possibility for attenuation of aging in human HSC.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.4
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据