Divisional History and Hematopoietic Stem Cell Function during Homeostasis

被引:101
作者
Qiu, Jiajing [1 ,3 ,4 ]
Papatsenko, Dmitri [1 ,3 ]
Niu, Xiaohong [1 ,3 ]
Schaniel, Christoph [2 ,3 ]
Moore, Kateri [1 ,3 ]
机构
[1] Icahn Sch Med Mt Sinai, Dept Dev & Regenerat Biol, New York, NY 10029 USA
[2] Icahn Sch Med Mt Sinai, Dept Pharmacol & Syst Therapeut, New York, NY 10029 USA
[3] Icahn Sch Med Mt Sinai, Black Family Stem Cell Inst, New York, NY 10029 USA
[4] Icahn Sch Med Mt Sinai, Grad Sch Biomed Sci, New York, NY 10029 USA
关键词
SELF-RENEWAL; CYCLE REGULATION; TGF-BETA; NICHE; PROLIFERATION; EXPRESSION; KINETICS; INSIGHTS; REVEALS; CANCER;
D O I
10.1016/j.stemcr.2014.01.016
中图分类号
Q813 [细胞工程];
学科分类号
摘要
We investigated the homeostatic behavior of hematopoietic stem and progenitor cells (HSPCs) temporally defined according to their divisional histories using an HSPC-specific GFP label-retaining system. We show that homeostatic hematopoietic stem cells (HSCs) lose repopulating potential after limited cell divisions. Once HSCs exit dormancy and accrue divisions, they also progressively lose the ability to return toG(0) and functional activities associated with quiescent HSCs. In addition, dormant HSPCs phenotypically defined as multipotent progenitor cells display robust stem cell activity upon transplantation, suggesting that temporal quiescence is a greater indicator of function than cell-surface phenotype. Our studies suggest that once homeostatic HSCs leave dormancy, they are slated for extinction. They self-renew phenotypically, but they lose self-renewal activity. As such, they question self-renewal as a characteristic of homeostatic, nonperturbed HSCs in contrast to self-renewal demonstrated under stress conditions.
引用
收藏
页码:473 / 490
页数:18
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