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The hemogenic competence of endothelial progenitors is restricted by Runx1 silencing during embryonic development.
Eliades, Alexia Wareing, Sarah Marinopoulou, Elli Fadlullah, Muhammad Z H Patel, Rahima Grabarek, J Plusa, B Lacaud, Georges Kouskoff, Valerie
Eliades, Alexia
Wareing, Sarah
Marinopoulou, Elli
Fadlullah, Muhammad Z H
Patel, Rahima
Grabarek, J
Plusa, B
Lacaud, Georges
Kouskoff, Valerie
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Abstract
It is now well-established that hematopoietic stem cells (HSCs) and progenitor cells originate from a specialized subset of endothelium, termed hemogenic endothelium (HE), via an endothelial-to-hematopoietic transition. However, the molecular mechanisms determining which endothelial progenitors possess this hemogenic potential are currently unknown. Here, we investigated the changes in hemogenic potential in endothelial progenitors at the early stages of embryonic development. Using an ETV2::GFP reporter mouse to isolate emerging endothelial progenitors, we observed a dramatic decrease in hemogenic potential between embryonic day (E)7.5 and E8.5. At the molecular level, Runx1 is expressed at much lower levels in E8.5 intra-embryonic progenitors, while Bmi1 expression is increased. Remarkably, the ectopic expression of Runx1 in these progenitors fully restores their hemogenic potential, as does the suppression of BMI1 function. Altogether, our data demonstrate that hemogenic competency in recently specified endothelial progenitors is restrained through the active silencing of Runx1 expression.
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Date
2016-06-07
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Article
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The hemogenic competence of endothelial progenitors is restricted by Runx1 silencing during embryonic development. 2016, 15 (10):2185-99 Cell Rep