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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3047414
- author
- Miharada, Kenichi
LU
; Karlsson, Göran
LU
; Rehn, Matilda
LU
; Rörby, Emma
LU
; Siva, Kavitha
LU
; Cammenga, Jörg
LU
and Karlsson, Stefan
LU
- organization
- publishing date
- 2012
- 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
- Wiley-Blackwell
- external identifiers
-
- wos:000312595400008
- pmid:22901256
- scopus:84865381995
- pmid:22901256
- 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
- 2016-04-04 09:27:29
- date last changed
- 2022-01-29 18:00:08
@article{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 = {{Wiley-Blackwell}},
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}},
doi = {{10.1111/j.1749-6632.2012.06564.x}},
volume = {{1266}},
year = {{2012}},
}