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

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Tumor necrosis factor restricts hematopoietic stem cell activity in mice: involvement of two distinct receptors. / Pronk, Kees-Jan; Veiby, Ole Petter; Bryder, David; Jacobsen, Sten Eirik W.

In: Journal of Experimental Medicine, Vol. 208, No. 8, 2011, p. 1563-1570.

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T1 - Tumor necrosis factor restricts hematopoietic stem cell activity in mice: involvement of two distinct receptors.

AU - Pronk, Kees-Jan

AU - Veiby, Ole Petter

AU - Bryder, David

AU - Jacobsen, Sten Eirik W

N1 - The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Stem Cell Aging (013212073), Stem Cell Center (013041110)

PY - 2011

Y1 - 2011

N2 - 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.

AB - 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.

U2 - 10.1084/jem.20110752

DO - 10.1084/jem.20110752

M3 - Article

C2 - 21768269

VL - 208

SP - 1563

EP - 1570

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 1540-9538

IS - 8

ER -