The positive regulatory effect of TGF-beta2 on primitive murine hemopoietic stem and progenitor cells is dependent on age, genetic background, and serum factors

TGF-beta is considered a negative regulator of hemopoietic stem and progenitor cells. We have previously shown that one TGF-beta isoform, TGF-beta2, is, in fact, a positive regulator of murine hemopoietic stem cell function in vivo. In vitro, TGF-beta2, but not TGF-beta1 and TGF-beta3, had a biphasi...

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Veröffentlicht in:The Journal of immunology (1950) 2004-08, Vol.173 (4), p.2486-2493
Hauptverfasser: Henckaerts, Els, Langer, Jessica C, Orenstein, Jonathan, Snoeck, Hans-Willem
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container_issue 4
container_start_page 2486
container_title The Journal of immunology (1950)
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creator Henckaerts, Els
Langer, Jessica C
Orenstein, Jonathan
Snoeck, Hans-Willem
description TGF-beta is considered a negative regulator of hemopoietic stem and progenitor cells. We have previously shown that one TGF-beta isoform, TGF-beta2, is, in fact, a positive regulator of murine hemopoietic stem cell function in vivo. In vitro, TGF-beta2, but not TGF-beta1 and TGF-beta3, had a biphasic dose response on the proliferation of purified lin-Sca1(++)kit(+) (LSK) cells, with a stimulatory effect at low concentrations, which was subject to mouse strain-dependent variation. In this study we report that the stimulatory effect of TGF-beta2 on the proliferation of LSK cells increases with age and after replicative stress in C57BL/6, but not in DBA/2, mice. The age-related changes in the TGF-beta2 effect correlated with life span in BXD recombinant strains. The stimulatory effect of TGF-beta2 on the proliferation of LSK cells requires one or more nonprotein, low m.w. factors present in fetal calf and mouse sera. The activity of this factor(s) in mouse serum increases with age. Taken together, our data suggest a role for TGF-beta2 and as yet unknown serum factors in the aging of the hemopoietic stem cell compartment and possibly in organismal aging.
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source MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection
subjects Aging
Animals
Bone Marrow Cells - cytology
Bone Marrow Cells - immunology
Dose-Response Relationship, Drug
Genetic Linkage
Hematopoiesis - genetics
Hematopoietic Stem Cells - drug effects
Hematopoietic Stem Cells - physiology
Longevity
Mice
Serum - immunology
Signal Transduction - drug effects
Signal Transduction - immunology
Transforming Growth Factor beta - immunology
Transforming Growth Factor beta - pharmacology
Transforming Growth Factor beta2
title The positive regulatory effect of TGF-beta2 on primitive murine hemopoietic stem and progenitor cells is dependent on age, genetic background, and serum factors
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