Professor of Molecular Medicine
Lund Stem Cell Center
Lund University Hospital
May 3 at 4 p.m. in Lecture hall, CRC, entr 72, SUS Malmö
Cripto, as a novel regulator of hematopoietic stem cells
Hematopoietic stem cells (HSC) are maintained in hypoxic niches in endosteal regions of bones. Here we demonstrate that Cripto and its receptor GRP78 are important regulators of HSC in the niche. Flow cytometry analyses revealed two distinct subpopulations of CD34ˆKSL 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, 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 number of GRP78+HSCs and reduced expression of Cripto in the endosteal niche.
Furthermore, the blocking of GRP78 induced a movement of HSCs from the endosteal to the central marrow area. These data suggest that Cripto/GRP78 signaling is a novel pathway that regulates HSC quiescence and maintains HSCs in hypoxia as an intermediary of HIF-1α.
Last updated: April 16, 2012
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