PDGFRβ Signaling Regulates Mural Cell Plasticity and Inhibits Fat Development

SummaryMural cells (pericytes and vascular smooth muscle cells) provide trophic and structural support to blood vessels. Vascular smooth muscle cells alternate between a synthetic/proliferative state and a differentiated/contractile state, but the dynamic states of pericytes are poorly understood. To explore the cues that regulate mural cell differentiation and homeostasis, we have generated conditional knockin mice with activating mutations at the PDGFRβ locus. We show that increased PDGFRβ signaling drives cell proliferation and downregulates differentiation genes in aortic vascular smooth muscle. Increased PDGFRβ signaling also induces a battery of immune response genes in pericytes and mesenchymal cells and inhibits differentiation of white adipocytes. Mural cells are emerging as multipotent progenitors of pathophysiological importance, and we identify PDGFRβ signaling as an important in vivo regulator of their progenitor potential.

Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (263 K)Download as PowerPoint slideHighlights► PDGF signaling in aortic mesenchyme opposes vascular smooth muscle differentiation ► Brain pericytes acquire an immune response phenotype when activated by PDGFRβ ► PDGF signaling inhibits the differentiation of white adipocytes in vivo and in vitro