Journal
BLOOD CELLS MOLECULES AND DISEASES
Volume 51, Issue 4, Pages 248-255Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bcmd.2013.07.010
Keywords
ETS transcription factors; Endothelial to hematopoietic transition; Gene regulatory network; Hemangioblast; Hematopoietic stem cell; Hematopoiesis
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Funding
- National Basic Research Program of China [2010CB945300, 2011CB943900]
- National Natural Science Foundation of China [30971678]
- CAS [XDA01010110]
- UK Medical Research Council
- MRC [MC_U137981013, MC_UU_12009/8] Funding Source: UKRI
- Medical Research Council [MC_UU_12009/8, G1000801a, MC_U137981013] Funding Source: researchfish
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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.
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