Laminin regulates PDGFR?(+) cell stemness and muscle development.

ABSTRACT: Muscle-resident PDGFR?(+) cells, which include pericytes and PW1(+) interstitial cells (PICs), play a dual role in muscular dystrophy. They can either undergo myogenesis to promote muscle regeneration or differentiate into adipocytes and other cells to compromise regeneration. How the differentiation and fate determination of PDGFR?(+) cells are regulated, however, remains unclear. Here, by utilizing a conditional knockout mouse line, we report that PDGFR?(+) cell-derived laminin inhibits their proliferation and adipogenesis, but is indispensable for their myogenesis. In addition, we show that laminin alone is able to partially reverse the muscle dystrophic phenotype in these mice at the molecular, structural and functional levels. Further RNAseq analysis reveals that laminin regulates PDGFR?(+) cell differentiation/fate determination via gpihbp1. These data support a critical role of laminin in the regulation of PDGFR?(+) cell stemness, identify an innovative target for future drug development and may provide an effective treatment for muscular dystrophy.

SUBMITTER: Yao Y 

PROVIDER: S-EPMC4857399 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature