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

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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Yao Y,Norris EH,Mason CE,Strickland S

doi

10.1038/ncomms11415

subject

Has Abstract

pub_date

2016-05-03 00:00:00

pages

11415

issn

2041-1723

pii

ncomms11415

journal_volume

7

pub_type

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