Global analysis of proliferation and cell cycle gene expression in the regulation of hematopoietic stem and progenitor cell fates.
Global analysis of proliferation and cell cycle gene expression in the regulation of hematopoietic stem and progenitor cell fates.
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DOI:
10.1084/jem.20050967
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发表时间:
2005-12-05
期刊:
影响因子:
--
通讯作者:
Weissman IL
中科院分区:
文献类型:
--
作者:
Passegué E;Wagers AJ;Giuriato S;Anderson WC;Weissman IL
Knowledge of the molecular networks controlling the proliferation and fate of hematopoietic stem cells (HSC) is essential to understand their function in maintaining blood cell production during normal hematopoiesis and upon clinical transplantation. Using highly purified stem and progenitor cell populations, we define the proliferation index and status of the cell cycle machinery at discrete stages of hematopoietic differentiation and during cytokine-mediated HSC mobilization. We identify distinct sets of cell cycle proteins that specifically associate with differentiation, self-renewal, and maintenance of quiescence in HSC and progenitor cells. Moreover, we describe a striking inequality of function among in vivo cycling and quiescent HSC by demonstrating that their long-term engraftment potential resides predominantly in the G0 fraction. These data provide a direct link between HSC proliferation and function and identify discrete molecular targets in regulating HSC cell fate decisions that could have implications for both the therapeutic use of HSC and the understanding of leukemic transformation.
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DOI:
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影响因子:
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