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

First Author  Pronk CJ Year  2011
Journal  J Exp Med Volume  208
Issue  8 Pages  1563-70
PubMed ID  21768269 Mgi Jnum  J:177605
Mgi Id  MGI:5295541 Doi  10.1084/jem.20110752
Citation  Pronk CJ, et al. (2011) Tumor necrosis factor restricts hematopoietic stem cell activity in mice: involvement of two distinct receptors. J Exp Med 208(8):1563-70
abstractText  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-alpha (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.
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