Abstract：
:Hematopoietic stem cells (HSCs) develop from a specialized subpopulation of endothelial cells known as hemogenic endothelium (HE). Although the HE origin of HSCs is now well established in different species, the signaling pathways that control this transition remain poorly understood. Here, we show that activation of retinoic acid (RA) signaling in aorta-gonad-mesonephros-derived HE ex vivo dramatically enhanced its HSC potential, whereas conditional inactivation of the RA metabolizing enzyme retinal dehydrogenase 2 in VE-cadherin expressing endothelial cells in vivo abrogated HSC development. Wnt signaling completely blocked the HSC inductive effects of RA modulators, whereas inhibition of the pathway promoted the development of HSCs in the absence of RA signaling. Collectively, these findings position RA and Wnt signaling as key regulators of HSC development and in doing so provide molecular insights that will aid in developing strategies for their generation from pluripotent stem cells.
journal_name
Celljournal_title
Cellauthors
Chanda B,Ditadi A,Iscove NN,Keller Gdoi
10.1016/j.cell.2013.08.055subject
Has Abstractpub_date
2013-09-26 00:00:00pages
215-27issue
1eissn
0092-8674issn
1097-4172pii
S0092-8674(13)01086-6journal_volume
155pub_type
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