ETS transcription factors in hematopoietic stem cell development
ETS transcription factors in hematopoietic stem cell development
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DOI：
10.1016/j.bcmd.2013.07.010
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发表时间：
2013-12-01
影响因子：
2.3
通讯作者：
Liu, Feng
中科院分区：
文献类型：
--
作者：
Ciau-Uitz, Aldo;Wang, Lu;Liu, Feng
造血干细胞(HSCs)对于维持造血系统是必不可少的。然而，这些细胞不能在体外维持或创造，而且对它们在胚胎发育过程中的生成知之甚少。许多转录因子和信号通路在HSC发育的不同阶段发挥着重要作用。Ets(‘E-26’)转录因子家族的成员被认为是控制造血的基因调控网络中的关键调节因子，包括造血干细胞的个体发育。值得注意的是，尽管所有的ETS转录因子都结合了相同的DNA共同序列，并观察到重叠的组织表达，但个别的ETS转录因子在HSCs的发展中发挥着独特的作用。此外，这些转录因子在整个发育过程中反复使用，它们的功能依赖于上下文，增加了研究它们的作用机制的挑战。至关重要的是，ETS因子在白血病等病理条件下也发挥作用，因此，破译它们的作用机制不仅将增强我们对正常造血的了解，还将为从多能干细胞体外创造ETS因子以及设计治疗恶性血细胞疾病的新治疗方法提供信息。在这篇综述中，我们总结了ETS转录因子在HSC发育中作用的主要发现，并讨论了它们控制造血的新机制。(C)2013 Elsevier Inc.保留所有权利。
Hematopoietic stem cells (HSCs) are essential for the maintenance of the hematopoietic system. However, these cells cannot be maintained or created in vitro, and very little is known about their generation during embryogenesis. Many transcription factors and signaling pathways play essential roles at various stages of HSC development. Members of the ETS ('E twenty-six') family of transcription factors are recognized as key regulators within the gene regulatory networks governing hematopoiesis, including the ontogeny of HSCs. Remarkably, although all ETS transcription factors bind the same DNA consensus sequence and overlapping tissue expression is observed, individual ETS transcription factors play unique roles in the development of HSCs. Also, these transcription factors are recurrently used throughout development and their functions are context-dependent, increasing the challenge of studying their mechanism of action. Critically, ETS factors also play roles under pathological conditions, such as leukemia and, therefore, deciphering their mechanism of action will not only enhance our knowledge of normal hematopoiesis, but also inform protocols for their creation in vitro from pluripotent stem cells and the design of new therapeutic approaches for the treatment of malignant blood cell diseases. In this review, we summarize the key findings on the roles of ETS transcription factors in HSC development and discuss novel mechanisms by which they could control hematopoiesis. (C) 2013 Elsevier Inc. All rights reserved.