The hemogenic competence of endothelial progenitors is restricted by Runx1 silencing during embryonic development.
Authors
Eliades, AlexiaWareing, Sarah
Marinopoulou, Elli
Fadlullah, Muhammad Z H
Patel, Rahima
Grabarek, J
Plusa, B
Lacaud, Georges
Kouskoff, Valerie
Affiliation
Cancer Research UK Stem Cell Hematopoiesis Group, Cancer Research UK Manchester Institute, The University of Manchester, Manchester M20 4BXIssue Date
2016-06-07
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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.Citation
The hemogenic competence of endothelial progenitors is restricted by Runx1 silencing during embryonic development. 2016, 15 (10):2185-99 Cell RepJournal
Cell ReportsDOI
10.1016/j.celrep.2016.05.001PubMed ID
27239041Type
ArticleLanguage
enISSN
2211-1247ae974a485f413a2113503eed53cd6c53
10.1016/j.celrep.2016.05.001
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