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:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Weissman IL
Weissman IL
中科院分区:
其他
文献类型:
--
作者:
Passegué E;Wagers AJ;Giuriato S;Anderson WC;Weissman IL

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控制造血干细胞(HSC)增殖和命运的分子网络的知识对于理解它们在正常造血期间和临床移植时维持血细胞产生的功能是必不可少的。使用高度纯化的干细胞和祖细胞群体,我们定义了增殖指数和状态的细胞周期机制在造血分化的离散阶段和在姜黄素介导的HSC动员。我们确定了不同的细胞周期蛋白,特别是与分化,自我更新,并在HSC和祖细胞的静止维持。此外,我们描述了一个显着的不平等的功能之间的体内循环和静止的HSC,证明他们的长期植入潜力主要驻留在G0级分。这些数据提供了HSC增殖和功能之间的直接联系,并确定了调节HSC细胞命运决定的离散分子靶点,这可能对HSC的治疗用途和白血病转化的理解都有影响。
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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