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Prmt5 is a regulator of muscle stem cell expansion in adult mice
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Prmt5 is a regulator of muscle stem cell expansion in adult mice
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Journal Article
Prmt5 is a regulator of muscle stem cell expansion in adult mice
2015
Overview
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.
Skeletal muscle satellite cells are important for muscle regeneration, but their regulatory mechanisms are largely unknown. Here the authors identify arginine methyltransferase Prmt5 as a key regulator of satellite cell maintenance and function in adult mice, and show that Prmt5 acts mainly but not exclusively on the cell cycle inhibitor p21.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Pub. Group
Subject
/ 42/41
/ Animals
/ Cell Differentiation - genetics
/ Cell Proliferation - genetics
/ Chromatin Immunoprecipitation
/ Cyclin-Dependent Kinase Inhibitor p21 - metabolism
/ Fluorescent Antibody Technique
/ Humanities and Social Sciences
/ Mice
/ Muscle Development - genetics
/ Muscle, Skeletal - pathology
/ Muscles
/ PAX7 Transcription Factor - metabolism
/ Protein Methyltransferases - genetics
/ Protein-Arginine N-Methyltransferases
/ Real-Time Polymerase Chain Reaction
/ Satellite Cells, Skeletal Muscle - cytology
/ Satellite Cells, Skeletal Muscle - metabolism
/ Science
