title: 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.
authors.affiliation: Laboratory of Neurobiology and Genetics, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA.|College of Pharmacy, University of Minnesota, 1110 Kirby Drive, Duluth, Minnesota 55812, USA.
authors.forename: Yao
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Laboratory of Neurobiology and Genetics, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA.
authors.forename: Erin H
authors.initials: EH
authors.lastname: Norris
authors.affiliation: Department of Physiology and Biophysics, Weill Cornell Medical College, New York, New York 10065, USA.|The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, New York, New York 10065, USA.|Tri-Institutional Training Program in Computational Biology and Medicine, New York, New York 10065, USA.|The Feil Family Brain and Mind Research Institute, New York, New York 10065, USA.
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Mason
authors.affiliation: Laboratory of Neurobiology and Genetics, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA.
authors.forename: Sidney
authors.initials: S
authors.lastname: Strickland
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D050156:Adipogenesis / Q000235:genetics; D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D005786:Gene Expression Regulation; D007797:Laminin / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D032342:Muscle Cells / Q000378:metabolism* / Q000473:pathology; D024510:Muscle Development / Q000235:genetics; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009136:Muscular Dystrophies / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020286:Pericytes / Q000166:cytology / Q000378:metabolism; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D018110:Receptors, Lipoprotein / Q000235:genetics / Q000378:metabolism*; D017423:Sequence Analysis, RNA; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism
chemical_list: C472779:GPI-HBP1 protein, mouse; D007797:Laminin; D018110:Receptors, Lipoprotein; D020797:Receptor, Platelet-Derived Growth Factor beta