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Developing HSCs become Notch independent by the end of maturation in the AGM region.

TitleDeveloping HSCs become Notch independent by the end of maturation in the AGM region.
Publication TypeJournal Article
Year of Publication2016
AuthorsSouilhol C, Lendinez JG, Rybtsov S, Murphy F, Wilson H, Hills D, Batsivari A, Binagui-Casas A, McGarvey AC, H MacDonald R, Kageyama R, Siebel C, Zhao S, Medvinsky AL
Date Published2016 Sep 22

The first definitive hematopoietic stem cells (dHSCs) in the mouse emerge in the dorsal aorta of the embryonic day (E) 10.5 to 11 aorta-gonad-mesonephros (AGM) region. Notch signaling is essential for early HSC development but is dispensable for the maintenance of adult bone marrow HSCs. How Notch signaling regulates HSC formation in the embryo is poorly understood. We demonstrate here that Notch signaling is active in E10.5 HSC precursors and involves both Notch1 and Notch2 receptors, but is gradually downregulated while they progress toward dHSCs at E11.5. This downregulation is accompanied by gradual functional loss of Notch dependency. Thus, as early as at final steps in the AGM region, HSCs begin acquiring the Notch independency characteristic of adult bone marrow HSCs as part of the maturation program. Our data indicate that fine stage-dependent tuning of Notch signaling may be required for the generation of definitive HSCs from pluripotent cells.

Alternate JournalBlood
PubMed ID27421959
PubMed Central IDPMC5034738
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