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

Details

Serval ID
serval:BIB_514D0918AC8E
Type
Article: article from journal or magazin.
Collection
Publications
Title
Developing HSCs become Notch independent by the end of maturation in the AGM region.
Journal
Blood
Author(s)
Souilhol C., Lendinez J.G., Rybtsov S., Murphy F., Wilson H., Hills D., Batsivari A., Binagui-Casas A., McGarvey A.C., MacDonald H.R., Kageyama R., Siebel C., Zhao S., Medvinsky A.
ISSN
1528-0020 (Electronic)
ISSN-L
0006-4971
Publication state
Published
Issued date
22/09/2016
Peer-reviewed
Oui
Volume
128
Number
12
Pages
1567-1577
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
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.

Keywords
Animals, Aorta/embryology, Aorta/metabolism, Cells, Cultured, Embryo, Mammalian/cytology, Embryo, Mammalian/metabolism, Gonads/embryology, Gonads/metabolism, Hematopoietic Stem Cell Transplantation, Hematopoietic Stem Cells/cytology, Hematopoietic Stem Cells/metabolism, Mesonephros/embryology, Mesonephros/metabolism, Mice, Mice, Inbred C57BL, Mice, Transgenic, Receptor, Notch2/metabolism, Signal Transduction, Stromal Cells/cytology, Stromal Cells/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
11/11/2016 9:50
Last modification date
08/05/2019 18:34
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