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Laminin regulates PDGFRβ(+) cell stemness and muscle development.

TitleLaminin regulates PDGFRβ(+) cell stemness and muscle development.
Publication TypeJournal Article
Year of Publication2016
AuthorsYao Y, Norris EH, Mason CE, Strickland S
JournalNat Commun
Volume7
Pagination11415
Date Published2016 May 03
ISSN2041-1723
KeywordsAdipocytes, Adipogenesis, Animals, Cell Differentiation, Cell Proliferation, Gene Expression Regulation, Laminin, Mice, Mice, Knockout, Muscle Cells, Muscle Development, Muscle, Skeletal, Muscular Dystrophies, Pericytes, Receptor, Platelet-Derived Growth Factor beta, Receptors, Lipoprotein, Sequence Analysis, RNA, Signal Transduction, Stem Cells
Abstract

Muscle-resident PDGFRβ(+) 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 PDGFRβ(+) cells are regulated, however, remains unclear. Here, by utilizing a conditional knockout mouse line, we report that PDGFRβ(+) 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 PDGFRβ(+) cell differentiation/fate determination via gpihbp1. These data support a critical role of laminin in the regulation of PDGFRβ(+) cell stemness, identify an innovative target for future drug development and may provide an effective treatment for muscular dystrophy.

DOI10.1038/ncomms11415
Alternate JournalNat Commun
PubMed ID27138650
PubMed Central IDPMC4857399
Grant ListR01 NS050537 / NS / NINDS NIH HHS / United States
NS050537 / NS / NINDS NIH HHS / United States