TY - JOUR
T1 - Laminin regulates PDGFRβ+ cell stemness and muscle development
AU - Yao, Yao
AU - Norris, Erin H.
AU - Mason, Christopher E.
AU - Strickland, Sidney
N1 - Publisher Copyright:
© 2016, Nature Publishing Group. All rights reserved.
PY - 2016/5/3
Y1 - 2016/5/3
N2 - 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.
AB - 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.
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U2 - 10.1038/ncomms11415
DO - 10.1038/ncomms11415
M3 - Article
C2 - 27138650
AN - SCOPUS:84966318810
SN - 2041-1723
VL - 7
JO - Nature communications
JF - Nature communications
M1 - 11415
ER -