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

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Author

Summary, in English

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.

Publishing year

2011

Language

English

Pages

1563-1570

Publication/Series

Journal of Experimental Medicine

Volume

208

Issue

8

Document type

Journal article

Publisher

Rockefeller University Press

Topic

  • Cell and Molecular Biology

Status

Published

Research group

  • Hematopoietic and immunologic developement

ISBN/ISSN/Other

  • ISSN: 1540-9538