Regulation of cell cycle in hematopoietic stem cells by the niche
Regulation of cell cycle in hematopoietic stem cells by the niche
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DOI：
10.4161/cc.3.12.1281
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发表时间：
2004-12-01
期刊：
影响因子：
4.3
通讯作者：
Suda, T
中科院分区：
文献类型：
--
作者：
Hirao, A;Arai, F;Suda, T
静止状态被认为是维持造血干细胞（hsc）不可缺少的特性。造血干细胞与其特定微环境（即干细胞壁龛）的相互作用对于造血干细胞的细胞周期调控至关重要。利用一种新的干细胞标志物侧群（Side Population， SP）监测造血干细胞的静止状态，发现造血干细胞的细胞周期状态是由微环境动态控制的。我们最近揭示了造血干细胞细胞周期受生态位调控的分子机制。表达受体酪氨酸激酶Tie2的造血干细胞粘附在BM生态位的成骨细胞（OBs）上。Tie2与其配体血管生成素-1 （ang1）的相互作用导致造血干细胞与基质细胞紧密粘附，从而维持造血干细胞的长期再生活性。因此，Tie2/Ang-1信号通路在BM生态位中维持hsc处于静止状态中起着关键作用。对干细胞细胞周期调控的认识将为再生医学的发展提供新的策略。
The quiescent state is thought to be an indispensable property for the maintenance of hematopoietic stem cells (HSCs). Interaction of HSCs with their particular microenvironments, known as the stem cell niches, is critical for cell cycle regulation of HSCs. Monitoring of the quiescence of HSCs using by a new stem cell marker, Side Population (SP), revealed that the cell cycle status of HSCs is dynamically controlled by the microenvironments. We have recently revealed a molecular mechanism in which cell cycle of HSCs is regulated by the niche. HSCs expressing the receptor tyrosine kinase Tie2 are adhere to osteoblasts (OBs) in the BM niche. The interaction of Tie2 and its ligand Angiopoietin-1 (Ang-1) leads to tight adhesion of HSCs to stromal cells, resulting in maintainance of long-term repopulating activity of HSCs. Thus, Tie2/Ang-1 signaling pathway plays a critical role in the maintenance of HSCs in a quiescent state in the BM niche. The understanding of cell cycle control in stem cells leads to development of new strategy for progress in regenerative medicine.