Platelet-derived growth factor receptor beta is required for embryonic specification and confinement of the adult white adipose lineage

ISCIENCE(2024)

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摘要
White adipose tissue (WAT) development and adult homeostasis rely on distinct adipocyte progenitor cells (APCs). While adult APCs are defined early during embryogenesis and generate adipocytes after WAT organogenesis, the mechanisms underlying adult adipose lineage determination and preservation remain undefined. Here, we uncover a critical role for platelet-derived growth factor receptor beta (PdgfrO) in identifying the adult APC lineage. Without PdgfrO, APCs lose their adipogenic competency to incite fibrotic tissue replacement and inflammation. Through lineage tracing analysis, we reveal that the adult APC lineage is lost and develops into macrophages when PdgfrO is deleted embryonically. More-over, to maintain the APC lineage, PdgfrO activation stimulates p38/MAPK phosphorylation to promote APC proliferation and maintains the APC state by phosphorylating peroxisome proliferator activated re-ceptor gamma (Ppary) at serine 112. Together, our findings identify a role for PdgfrO acting as a rheostat for adult adipose lineage confinement to prevent unintended lineage switches.
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