Journal
DEVELOPMENTAL CELL
Volume 20, Issue 6, Pages 815-826Publisher
CELL PRESS
DOI: 10.1016/j.devcel.2011.04.019
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Funding
- American Cancer Society
- Oklahoma Medical Research Foundation
- National Institute of Child Health and Human Development [RO1HD24875, R37HD25326]
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Mural 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 PDGFR beta locus. We show that increased PDGFR beta signaling drives cell proliferation and downregulates differentiation genes in aortic vascular smooth muscle. Increased PDGFR beta 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 PDGFR beta signaling as an important in vivo regulator of their progenitor potential.
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