PDGFRα controls the balance of stromal and adipogenic cells during adipose tissue organogenesis

Adipose tissue is distributed in depots throughout the body with specialized roles in energy storage and thermogenesis. PDGFR alpha is a marker of adipocyte precursors, and increased PDGFRa activity causes adipose tissue fibrosis in adult mice. However, the function of PDGFRa during adipose tissue organogenesis is unknown. Here, by analyzing mice with juxtamembrane or kinase domain point mutations that increase PDGFRa activity (V561D or D842V), we found that PDGFRa activation inhibits embryonic white adipose tissue organogenesis in a tissue-autonomous manner. By lineage tracing analysis, we also found that collagen-expressing precursor fibroblasts differentiate into white adipocytes in the embryo. PDGFRa inhibited the formation of adipocytes from these precursors while favoring the formation of stromal fibroblasts. This imbalance between adipocytes and stromal cells was accompanied by overexpression of the cell fate regulator Zfp521. PDGFRa activation also inhibited the formation of juvenile beige adipocytes in the inguinal fat pad. Our data highlight the importance of balancing stromal versus adipogenic cell expansion during white adipose tissue development, with PDGFRa activity coordinating this crucial process in the embryo.