Cripto Regulates Hematopoietic Stem Cells as a Hypoxic-Niche-Related Factor through Cell Surface Receptor GRP78.
Författare
Summary, in English
Hematopoietic stem cells (HSCs) are maintained in hypoxic niches in endosteal regions of bones. Here we demonstrate that Cripto and its receptor GRP78 are important regulators of HSCs in the niche. Flow cytometry analyses revealed two distinct subpopulations of CD34(-)KSL cells based on the expression of GRP78, and these populations showed different reconstitution potential in transplantation assays. GRP78(+)HSCs mainly reside in the endosteal area, are more hypoxic, and exhibit a lower mitochondrial potential, and their HSC capacity was maintained in vitro by Cripto through induction of higher glycolytic activity. Additionally, HIF-1α KO mice have decreased numbers of GRP78(+)HSCs and reduced expression of Cripto in the endosteal niche. Furthermore, blocking GRP78 induced a movement of HSCs from the endosteal to the central marrow area. These data suggest that Cripto/GRP78 signaling is an important pathway that regulates HSC quiescence and maintains HSCs in hypoxia as an intermediary of HIF-1α.
Avdelning/ar
Publiceringsår
2011
Språk
Engelska
Sidor
330-344
Publikation/Tidskrift/Serie
Cell Stem Cell
Volym
9
Issue
4
Länkar
Dokumenttyp
Artikel i tidskrift
Förlag
Cell Press
Ämne
- Cell Biology
Status
Published
Forskningsgrupp
- Hematopoiesis and Gene Therapy
- Stem Cell Metabolism
ISBN/ISSN/Övrigt
- ISSN: 1934-5909