First Author | Sun C | Year | 2020 |
Journal | Cell Stem Cell | Volume | 26 |
Issue | 5 | Pages | 707-721.e5 |
PubMed ID | 32229310 | Mgi Jnum | J:306160 |
Mgi Id | MGI:6710943 | Doi | 10.1016/j.stem.2020.03.004 |
Citation | Sun C, et al. (2020) Mosaic Mutant Analysis Identifies PDGFRalpha/PDGFRbeta as Negative Regulators of Adipogenesis. Cell Stem Cell 26(5):707-721.e5 |
abstractText | Adipocyte progenitors (APs) express platelet-derived growth factor receptors (PDGFRs), PDGFRalpha and PDGFRbeta. Elevated PDGFRalpha signaling inhibits adipogenesis and promotes fibrosis; however, the function of PDGFRs in APs remains unclear. We combined lineage tracing and functional analyses in a sequential dual-recombinase approach that creates mosaic Pdgfr mutant cells by Cre/lox recombination with a linked Flp/frt reporter to track individual cell fates. Using mosaic lineage labeling, we show that adipocytes are derived from the Pdgfra lineage during postnatal growth and adulthood. In contrast, adipocytes are only derived from the mosaic Pdgfrb lineage during postnatal growth. Functionally, postnatal mosaic deletion of PDGFRalpha enhances adipogenesis and adult deletion enhances beta3-adrenergic-receptor-induced beige adipocyte formation. Mosaic deletion of PDGFRbeta also enhances white, brown, and beige adipogenesis. These data show that both PDGFRs are cell-autonomous inhibitors of adipocyte differentiation and implicate downregulation of PDGF signaling as a critical event in the transition from AP to adipocyte. |