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Tumor necrosis factor restricts hematopoietic stem cell activity in mice: involvement of two distinct receptors.

Pronk, Kees-Jan LU ; Veiby, Ole Petter; Bryder, David LU and Jacobsen, Sten Eirik W LU (2011) In Journal of Experimental Medicine 208(8). p.1563-1570
Abstract
Whereas maintenance of hematopoietic stem cells (HSCs) is a requisite for life, uncontrolled expansion of HSCs might enhance the propensity for leukemic transformation. Accordingly, HSC numbers are tightly regulated. The identification of physical cellular HSC niches has underscored the importance of extrinsic regulators of HSC homeostasis. However, whereas extrinsic positive regulators of HSCs have been identified, opposing extrinsic repressors of HSC expansion in vivo have yet to be described. Like many other acute and chronic inflammatory diseases, bone marrow (BM) failure syndromes are associated with tumor necrosis factor-α (TNF) overexpression. However, the in vivo relevance of TNF in the regulation of HSCs has remained unclear. Of... (More)
Whereas maintenance of hematopoietic stem cells (HSCs) is a requisite for life, uncontrolled expansion of HSCs might enhance the propensity for leukemic transformation. Accordingly, HSC numbers are tightly regulated. The identification of physical cellular HSC niches has underscored the importance of extrinsic regulators of HSC homeostasis. However, whereas extrinsic positive regulators of HSCs have been identified, opposing extrinsic repressors of HSC expansion in vivo have yet to be described. Like many other acute and chronic inflammatory diseases, bone marrow (BM) failure syndromes are associated with tumor necrosis factor-α (TNF) overexpression. However, the in vivo relevance of TNF in the regulation of HSCs has remained unclear. Of considerable relevance for normal hematopoiesis and in particular BM failure syndromes, we herein demonstrate that TNF is a cell-extrinsic and potent endogenous suppressor of normal HSC activity in vivo in mice. These effects of TNF involve two distinct TNF receptors. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Experimental Medicine
volume
208
issue
8
pages
1563 - 1570
publisher
Rockefeller University Press
external identifiers
  • wos:000293441500001
  • pmid:21768269
  • scopus:79961138056
ISSN
1540-9538
DOI
10.1084/jem.20110752
language
English
LU publication?
yes
id
52ba4948-b7c0-4640-970e-a3efbdd65e1b (old id 2058522)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21768269?dopt=Abstract
date added to LUP
2011-08-01 20:09:59
date last changed
2017-11-19 03:42:18
@article{52ba4948-b7c0-4640-970e-a3efbdd65e1b,
  abstract     = {Whereas maintenance of hematopoietic stem cells (HSCs) is a requisite for life, uncontrolled expansion of HSCs might enhance the propensity for leukemic transformation. Accordingly, HSC numbers are tightly regulated. The identification of physical cellular HSC niches has underscored the importance of extrinsic regulators of HSC homeostasis. However, whereas extrinsic positive regulators of HSCs have been identified, opposing extrinsic repressors of HSC expansion in vivo have yet to be described. Like many other acute and chronic inflammatory diseases, bone marrow (BM) failure syndromes are associated with tumor necrosis factor-α (TNF) overexpression. However, the in vivo relevance of TNF in the regulation of HSCs has remained unclear. Of considerable relevance for normal hematopoiesis and in particular BM failure syndromes, we herein demonstrate that TNF is a cell-extrinsic and potent endogenous suppressor of normal HSC activity in vivo in mice. These effects of TNF involve two distinct TNF receptors.},
  author       = {Pronk, Kees-Jan and Veiby, Ole Petter and Bryder, David and Jacobsen, Sten Eirik W},
  issn         = {1540-9538},
  language     = {eng},
  number       = {8},
  pages        = {1563--1570},
  publisher    = {Rockefeller University Press},
  series       = {Journal of Experimental Medicine},
  title        = {Tumor necrosis factor restricts hematopoietic stem cell activity in mice: involvement of two distinct receptors.},
  url          = {http://dx.doi.org/10.1084/jem.20110752},
  volume       = {208},
  year         = {2011},
}