Cell cycle regulation in hematopoietic stem/progenitor cells.
Cell cycle regulation in hematopoietic stem/progenitor cells.
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DOI：
10.3923/jbs.2005.50.60
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发表时间：
2004
期刊：
影响因子：
4.3
通讯作者：
S. Ezoe;I. Matsumura;Yusuke Satoh;Hirokazu Tanaka;Y. Kanakura
中科院分区：
文献类型：
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作者：
S. Ezoe;I. Matsumura;Yusuke Satoh;Hirokazu Tanaka;Y. Kanakura
造血干细胞(HSCs)具有多能性和自我更新能力。为了既保持成熟血细胞的供应，又不在生物体的整个生命周期中耗尽HSCs，大多数HSCs保持静止，只有有限数量的HSCs进入细胞周期。在HSCs中，细胞周期受到细胞因子以及与基质细胞和骨髓微环境中的细胞外基质(ECM)相互作用等外部因素的关键调控。此外，在HSC中表达的内源性转录因子，包括c-Myb、GATA-2、Hox家族蛋白和Bmi-1，也通过影响基因转录来控制其生长。根据细胞周期调控的特殊作用，p21WAF1(P21)和p27KIP1(P27)分别维持HSC和祖细胞的静止，从而控制其可用的池大小。此外，p16INK4A(P16)和p15INK4b(P15)被认为是肿瘤抑制基因，因为它们的失活和/或缺失在各种类型的血液系统恶性肿瘤中都可以观察到。这些结果表明，为了维持正常的造血，需要适当的细胞周期控制，特别是在干细胞/祖细胞的早期阶段。
Hematopoietic stem cells (HSCs) are characterized by pluripotentiality and a capacity for self-renewal. In order to both maintain a supply of mature blood cells and not to exhaust HSCs throughout the lifespan of the organism, most HSCs remain quiescent and only a limited number enter the cell cycle. In HSCs, the cell cycle is crucially regulated by external factors such as cytokines and interactions with stromal cells and the extracellular matrix (ECM) in the bone marrow (BM) microenvironment. In addition, intrinsic transcription factors expressed in HSCs, including c-Myb, GATA-2, HOX family proteins, and Bmi-1, also control their growth through their effect on gene transcription. In terms of the particular roles in regulation of the cell-cycle, p21WAF1 (p21) and p27KIP1 (p27) were shown to maintain the quiescence of HSCs and of progenitor cells, respectively, thereby governing their available pool sizes. Also, p16INK4A (p16) and p15INK4B (p15) are thought to act as tumor suppressors, since their inactivation and/or deletion are observable in various types of hematologic malignancies. These results make evident that appropriate cell cycle control, particularly at the early stage of stem/progenitor cells, is required for maintaining normal hematopoiesis.