title: Prmt5 is a regulator of muscle stem cell expansion in adult mice.
abstract: Skeletal muscle stem cells (MuSC), also called satellite cells, are indispensable for maintenance and regeneration of adult skeletal muscles. Yet, a comprehensive picture of the regulatory events controlling the fate of MuSC is missing. Here, we determine the proteome of MuSC to design a loss-of-function screen, and identify 120 genes important for MuSC function including the arginine methyltransferase Prmt5. MuSC-specific inactivation of Prmt5 in adult mice prevents expansion of MuSC, abolishes long-term MuSC maintenance and abrogates skeletal muscle regeneration. Interestingly, Prmt5 is dispensable for proliferation and differentiation of Pax7(+) myogenic progenitor cells during mouse embryonic development, indicating significant differences between embryonic and adult myogenesis. Mechanistic studies reveal that Prmt5 controls proliferation of adult MuSC by direct epigenetic silencing of the cell cycle inhibitor p21. We reason that Prmt5 generates a poised state that keeps MuSC in a standby mode, thus allowing rapid MuSC amplification under disease conditions.
authors.affiliation: Department of Cardiac Development and Remodeling, Max-Planck Institute for Heart and Lung Research, Bad Nauheim 61231, Germany.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Cardiac Development and Remodeling, Max-Planck Institute for Heart and Lung Research, Bad Nauheim 61231, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Günther
authors.affiliation: Department of Cardiac Development and Remodeling, Max-Planck Institute for Heart and Lung Research, Bad Nauheim 61231, Germany.
authors.forename: Mario
authors.initials: M
authors.lastname: Looso
authors.affiliation: Department of Cardiac Development and Remodeling, Max-Planck Institute for Heart and Lung Research, Bad Nauheim 61231, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Künne
authors.affiliation: Department of Cardiac Development and Remodeling, Max-Planck Institute for Heart and Lung Research, Bad Nauheim 61231, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Krüger
authors.affiliation: Department of Cardiac Development and Remodeling, Max-Planck Institute for Heart and Lung Research, Bad Nauheim 61231, Germany.
authors.forename: Johnny
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Cardiac Development and Remodeling, Max-Planck Institute for Heart and Lung Research, Bad Nauheim 61231, Germany.
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Cardiac Development and Remodeling, Max-Planck Institute for Heart and Lung Research, Bad Nauheim 61231, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Braun
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics*; D047369:Chromatin Immunoprecipitation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D044127:Epigenesis, Genetic; D005455:Fluorescent Antibody Technique; D020868:Gene Silencing; D008279:Magnetic Resonance Imaging; D013058:Mass Spectrometry; D051379:Mice; D018345:Mice, Knockout; D024510:Muscle Development / Q000235:genetics*; D018482:Muscle, Skeletal / Q000166:cytology / Q000473:pathology; D051763:PAX7 Transcription Factor / Q000378:metabolism; D011496:Protein Methyltransferases / Q000235:genetics*; D011484:Protein-Arginine N-Methyltransferases; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D051763:PAX7 Transcription Factor; C497322:Pax7 protein, mouse; D020543:Proteome; D011496:Protein Methyltransferases; C498518:Prmt5 protein, mouse; D011484:Protein-Arginine N-Methyltransferases