BMP and Hedgehog regulate distinct AGM hematopoietic stem cells ex vivo

Mihaela Crisan, Parham Solaimani Kartalaei, Alex Neagu, Sofia Karkanpouna, Tomoko Yamada-Inagawa, Caterina Purini, Chris Vink, Reiner van der Linden, Wilfred Van Ijcken, Susana Chuva de Sousa Lopes, Rui Monteiro, Christine L. Mummery, Elaine Dzierzak

Research output: Contribution to journalArticlepeer-review

Abstract

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/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/Smadactivated 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 signalling 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 signalling molecules in the microenvironment.
Original languageEnglish
JournalStem Cell Reports
DOIs
Publication statusPublished - 25 Feb 2016

Keywords

  • hematopoietic stem/progenitor cells
  • HPSCs
  • AGM
  • BMP
  • Hh
  • VEGF
  • development
  • Hematopoiesis

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