PDGF signaling regulates the adipocyte-to-fibroblast transition in wound healing

Adipocytes are plastic cells with the ability to transition into fibroblast-like cells during tissue repair or physiological remodeling. It is unclear how such transitions are regulated and whether they exemplify cell plasticity or merely a transient suppression of adipocyte features. Fibroblasts express platelet-derived growth factor receptors (Pdgfra and Pdgfrb), while adipocytes express adiponectin (Adipoq). Here, we use two-step lineage tracing to label Pdgfra⁺ and Pdgfrb⁺ cells originating from Adipoq⁺ adipocytes. Adipocyte-derived Pdgfr⁺ cells (ADPCs) are induced adjacent to skin wounds and contribute to the wound fibroblast population. ADPCs lose adipocyte characteristics and acquire fibroblast characteristics, including collagen expression, smooth muscle actin expression, and cell proliferation. Active PDGFRα signaling in ADPCs increases cell proliferation and improves wound angiogenesis and re-epithelialization, while deletion of Pdgfra has the opposite effect. Wound ADPCs persist as fibroblast-like cells after completion of wound healing, indicating an enduring change rather than a transient downregulation of adipocyte characteristics.