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Hematopoietic stem cells are regulated by Cripto, as an intermediary of HIF-1α in the hypoxic bone marrow niche.

Miharada, Kenichi LU ; Karlsson, Göran LU ; Rehn, Matilda LU ; Rörby, Emma LU ; Siva, Kavitha LU ; Cammenga, Jörg LU and Karlsson, Stefan LU (2012) In Annals of the New York Academy of Sciences 1266(1). p.55-62
Abstract
Cripto has been known as an embryonic stem (ES)- or tumor-related soluble/cell membrane protein. In this study, we demonstrated that Cripto has a role as an important regulatory factor for hematopoietic stem cells (HSCs). Recombinant Cripto sustained the reconstitution ability of HSCs in vitro. Flow cytometry analysis uncovered that GRP78, one of the candidate receptors for Cripto, was expressed on a subset of HSCs and could distinguish dormant/myeloid-biased HSCs and active/lymphoid-biased HSCs. Cripto is expressed in hypoxic endosteal niche cells where GRP78(+) HSCs mainly reside. Proteomics analysis revealed that Cripto-GRP78 binding stimulates glycolytic metabolism-related proteins and results in lower mitochondrial potential in HSCs.... (More)
Cripto has been known as an embryonic stem (ES)- or tumor-related soluble/cell membrane protein. In this study, we demonstrated that Cripto has a role as an important regulatory factor for hematopoietic stem cells (HSCs). Recombinant Cripto sustained the reconstitution ability of HSCs in vitro. Flow cytometry analysis uncovered that GRP78, one of the candidate receptors for Cripto, was expressed on a subset of HSCs and could distinguish dormant/myeloid-biased HSCs and active/lymphoid-biased HSCs. Cripto is expressed in hypoxic endosteal niche cells where GRP78(+) HSCs mainly reside. Proteomics analysis revealed that Cripto-GRP78 binding stimulates glycolytic metabolism-related proteins and results in lower mitochondrial potential in HSCs. Furthermore, conditional knockout mice for HIF-1α, a master regulator of hypoxic responses, showed reduced Cripto expression and decreased GRP78(+) HSCs in the endosteal niche area. Thus, Cripto-GRP78 is a novel HSC regulatory signal mainly working in the hypoxic niche. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
in
Annals of the New York Academy of Sciences
volume
1266
issue
1
pages
55 - 62
publisher
New York Academy of Sciences
external identifiers
  • WOS:000312595400008
  • PMID:22901256
  • Scopus:84865381995
ISSN
0077-8923
DOI
10.1111/j.1749-6632.2012.06564.x
language
English
LU publication?
yes
id
1509898a-b37e-46e2-b074-d2ca0827e6f4 (old id 3047414)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22901256?dopt=Abstract
date added to LUP
2012-09-05 19:53:38
date last changed
2016-11-13 04:28:40
@misc{1509898a-b37e-46e2-b074-d2ca0827e6f4,
  abstract     = {Cripto has been known as an embryonic stem (ES)- or tumor-related soluble/cell membrane protein. In this study, we demonstrated that Cripto has a role as an important regulatory factor for hematopoietic stem cells (HSCs). Recombinant Cripto sustained the reconstitution ability of HSCs in vitro. Flow cytometry analysis uncovered that GRP78, one of the candidate receptors for Cripto, was expressed on a subset of HSCs and could distinguish dormant/myeloid-biased HSCs and active/lymphoid-biased HSCs. Cripto is expressed in hypoxic endosteal niche cells where GRP78(+) HSCs mainly reside. Proteomics analysis revealed that Cripto-GRP78 binding stimulates glycolytic metabolism-related proteins and results in lower mitochondrial potential in HSCs. Furthermore, conditional knockout mice for HIF-1α, a master regulator of hypoxic responses, showed reduced Cripto expression and decreased GRP78(+) HSCs in the endosteal niche area. Thus, Cripto-GRP78 is a novel HSC regulatory signal mainly working in the hypoxic niche.},
  author       = {Miharada, Kenichi and Karlsson, Göran and Rehn, Matilda and Rörby, Emma and Siva, Kavitha and Cammenga, Jörg and Karlsson, Stefan},
  issn         = {0077-8923},
  language     = {eng},
  number       = {1},
  pages        = {55--62},
  publisher    = {ARRAY(0x90adb98)},
  series       = {Annals of the New York Academy of Sciences},
  title        = {Hematopoietic stem cells are regulated by Cripto, as an intermediary of HIF-1α in the hypoxic bone marrow niche.},
  url          = {http://dx.doi.org/10.1111/j.1749-6632.2012.06564.x},
  volume       = {1266},
  year         = {2012},
}