Abstract:
:Adipocyte progenitors (APs) express platelet-derived growth factor receptors (PDGFRs), PDGFRα and PDGFRβ. Elevated PDGFRα 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 PDGFRα enhances adipogenesis and adult deletion enhances β3-adrenergic-receptor-induced beige adipocyte formation. Mosaic deletion of PDGFRβ 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.
journal_name
Cell Stem Celljournal_title
Cell stem cellauthors
Sun C,Sakashita H,Kim J,Tang Z,Upchurch GM,Yao L,Berry WL,Griffin TM,Olson LEdoi
10.1016/j.stem.2020.03.004subject
Has Abstractpub_date
2020-05-07 00:00:00pages
707-721.e5issue
5eissn
1934-5909issn
1875-9777pii
S1934-5909(20)30096-5journal_volume
26pub_type
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