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Cripto Regulates Hematopoietic Stem Cells as a Hypoxic-Niche-Related Factor through Cell Surface Receptor GRP78.

Miharada, Kenichi LU ; Karlsson, Göran LU ; Rehn, Matilda LU ; Rörby, Emma LU ; Siva, Kavitha LU ; Cammenga, Jörg LU and Karlsson, Stefan LU (2011) In Cell Stem Cell 9(4). p.330-344
Abstract
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.... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cell Stem Cell
volume
9
issue
4
pages
330 - 344
publisher
Cell Press
external identifiers
  • wos:000296041200011
  • pmid:21982233
  • scopus:80053926733
ISSN
1934-5909
DOI
10.1016/j.stem.2011.07.016
language
English
LU publication?
yes
id
10c8951d-ba34-4740-8b0c-eb63701fa732 (old id 2200726)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21982233?dopt=Abstract
date added to LUP
2011-11-02 08:29:07
date last changed
2017-10-01 04:59:21
@article{10c8951d-ba34-4740-8b0c-eb63701fa732,
  abstract     = {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.},
  author       = {Miharada, Kenichi and Karlsson, Göran and Rehn, Matilda and Rörby, Emma and Siva, Kavitha and Cammenga, Jörg and Karlsson, Stefan},
  issn         = {1934-5909},
  language     = {eng},
  number       = {4},
  pages        = {330--344},
  publisher    = {Cell Press},
  series       = {Cell Stem Cell},
  title        = {Cripto Regulates Hematopoietic Stem Cells as a Hypoxic-Niche-Related Factor through Cell Surface Receptor GRP78.},
  url          = {http://dx.doi.org/10.1016/j.stem.2011.07.016},
  volume       = {9},
  year         = {2011},
}