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 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.
Carl C. Icahn Center for Gene Therapy and Molecular Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA.
Els
E
Henckaerts
Jessica C
JC
Langer
Jonathan
J
Orenstein
Hans-Willem
HW
Snoeck
D000375:Aging; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D008040:Genetic Linkage; D006410:Hematopoiesis / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000502:physiology*; D008136:Longevity; D051379:Mice; D044967:Serum / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000276:immunology* / Q000494:pharmacology; D053781:Transforming Growth Factor beta2
D016212:Transforming Growth Factor beta; D053781:Transforming Growth Factor beta2