Mosaic Mutant Analysis Identifies PDGFRα/PDGFRβ as Negative Regulators of Adipogenesis.

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 Cell

journal_title

Cell stem cell

authors

Sun C,Sakashita H,Kim J,Tang Z,Upchurch GM,Yao L,Berry WL,Griffin TM,Olson LE

doi

10.1016/j.stem.2020.03.004

subject

Has Abstract

pub_date

2020-05-07 00:00:00

pages

707-721.e5

issue

5

eissn

1934-5909

issn

1875-9777

pii

S1934-5909(20)30096-5

journal_volume

26

pub_type

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