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Publication : Retinoic acid signaling is essential for embryonic hematopoietic stem cell development.

First Author  Chanda B Year  2013
Journal  Cell Volume  155
Issue  1 Pages  215-27
PubMed ID  24074870 Mgi Jnum  J:214485
Mgi Id  MGI:5603033 Doi  10.1016/j.cell.2013.08.055
Citation  Chanda B, et al. (2013) Retinoic acid signaling is essential for embryonic hematopoietic stem cell development. Cell 155(1):215-27
abstractText  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.
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