| First Author | Avagyan S | Year | 2011 |
| Journal | Blood | Volume | 118 |
| Issue | 23 | Pages | 6078-86 |
| PubMed ID | 21967974 | Mgi Jnum | J:179097 |
| Mgi Id | MGI:5301062 | Doi | 10.1182/blood-2011-07-365080 |
| Citation | Avagyan S, et al. (2011) Quantitative trait mapping reveals a regulatory axis involving peroxisome proliferator-activated receptors, PRDM16, transforming growth factor-beta2 and FLT3 in hematopoiesis. Blood 118(23):6078-86 |
| abstractText | Hematopoiesis is the process whereby BM HSCs renew to maintain their number or to differentiate into committed progenitors to generate all blood cells. One approach to gain mechanistic insight into this complex process is the investigation of quantitative genetic variation in hematopoietic function among inbred mouse strains. We previously showed that TGF-beta2 is a genetically determined positive regulator of hematopoiesis. In the presence of unknown nonprotein serum factors TGF-beta2, but not TGF-beta1 or -beta3, enhances progenitor proliferation in vitro, an effect that is subject to mouse strain-dependent variation mapping to a locus on chr.4, Tb2r1. TGF-beta2-deficient mice show hematopoietic defects, demonstrating the physiologic role of this cytokine. Here, we show that TGF-beta2 specifically and predominantly cell autonomously enhances signaling by FLT3 in vitro and in vivo. A coding polymorphism in Prdm16 (PR-domain-containing 16) underlies Tb2r1 and differentially regulates transcriptional activity of peroxisome proliferator-activated receptor-gamma (PPARgamma), identifying lipid PPAR ligands as the serum factors required for regulation of FLT3 signaling by TGF-beta2. We furthermore show that PPARgamma agonists play a FLT3-dependent role in stress responses of progenitor cells. These observations identify a novel regulatory axis that includes PPARs, Prdm16, and TGF-beta2 in hematopoiesis. |
