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BMP and Hedgehog Regulate Distinct AGM Hematopoietic Stem Cells Ex Vivo.

TitleBMP and Hedgehog Regulate Distinct AGM Hematopoietic Stem Cells Ex Vivo.
Publication TypeJournal Article
Year of Publication2016
AuthorsCrisan M, Kartalaei PSolaimani, Neagu A, Karkanpouna S, Yamada-Inagawa T, Purini C, Vink CS, van der Linden R, van IJcken W, Lopes SMChuva de, Monteiro R, Mummery C, Dzierzak E
JournalStem Cell Reports
Date Published2016 Mar 8

Hematopoietic stem cells (HSC), the self-renewing cells of the adult blood differentiation hierarchy, are generated during embryonic stages. The first HSCs are produced in the aorta-gonad-mesonephros (AGM) region of the embryo through endothelial to a hematopoietic transition. BMP4 and Hedgehog affect their production and expansion, but it is unknown whether they act to affect the same HSCs. In this study using the BRE GFP reporter mouse strain that identifies BMP/Smad-activated cells, we find that the AGM harbors two types of adult-repopulating HSCs upon explant culture: One type is BMP-activated and the other is a non-BMP-activated HSC type that is indirectly controlled by Hedgehog signaling through the VEGF pathway. Transcriptomic analyses demonstrate that the two HSC types express distinct but overlapping genetic programs. These results revealing the bifurcation in HSC types at early embryonic stages in the AGM explant model suggest that their development is dependent upon the signaling molecules in the microenvironment.

Alternate JournalStem Cell Reports
PubMed ID26923823
PubMed Central IDPMC4788785
Grant ListR01 DK054077 / DK / NIDDK NIH HHS / United States
R37 DK054077 / DK / NIDDK NIH HHS / United States
R037 DK54077 / DK / NIDDK NIH HHS / United States
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