Regulation of Hematopoiesis and Hematological Disease by TGF-β Family Signaling Molecules
Regulation of Hematopoiesis and Hematological Disease by TGF-β Family Signaling Molecules
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DOI：
10.1101/cshperspect.a027987
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发表时间：
2017-09-01
影响因子：
7.2
通讯作者：
Hirao, Atsushi
中科院分区：
文献类型：
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作者：
Naka, Kazuhito;Hirao, Atsushi
在个体的一生中，造血干细胞（HSC）通过精确生成成熟血细胞来维持正常造血的稳态。在小鼠中的许多遗传学研究表明，干细胞静止对于维持体内原始长期HSC至关重要。在这篇综述中，我们首先研究了转化生长因子β（TGF-β）和相关信号分子的关键作用，不仅调节这些分子的细胞生长抑制作用，而且还管理HSC在其体内微环境生态位的自我更新能力。其次，我们讨论了目前的证据表明，TGF-β信号转导在造血系统疾病中具有双重功能。特别是，我们研究的悖论，虽然内在的TGF-β信号是必不可少的调节生存和治疗慢性髓性白血病（CML）干细胞的抗性，基因的变化，废除TGF-β信号可能会导致几个恶性血液病的发展。
Throughout the lifetime of an individual, hematopoietic stem cells (HSCs) maintain the homeostasis of normal hematopoiesis through the precise generation of mature blood cells. Numerous genetic studies in mice have shown that stem-cell quiescence is critical for sustaining primitive long-term HSCs in vivo. In this review, we first examine the crucial roles of transforming growth factor beta (TGF-beta) and related signaling molecules in not only regulating the well-known cytostatic effects of these molecules but also governing the self-renewal capacity of HSCs in their in vivo microenvironmental niche. Second, we discuss the current evidence indicating that TGF-beta signaling has a dual function in disorders of the hematopoietic system. In particular, we examine the paradox that, although intrinsic TGF-beta signaling is essential for regulating the survival and resistance to therapy of chronic myelogenous leukemia (CML) stem cells, genetic changes that abrogate TGF-beta signaling can lead to the development of several hematological malignancies.