[PDF][PDF] Mosaic mutant analysis identifies PDGFRα/PDGFRβ as negative regulators of adipogenesis

C Sun, H Sakashita, J Kim, Z Tang, GM Upchurch… - Cell Stem Cell, 2020 - cell.com
C Sun, H Sakashita, J Kim, Z Tang, GM Upchurch, L Yao, WL Berry, TM Griffin, LE Olson
Cell Stem Cell, 2020cell.com
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 …
Summary
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.
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