title: Polycomb EZH2 controls self-renewal and safeguards the transcriptional identity of skeletal muscle stem cells.
abstract: Satellite cells (SCs) sustain muscle growth and empower adult skeletal muscle with vigorous regenerative abilities. Here, we report that EZH2, the enzymatic subunit of the Polycomb-repressive complex 2 (PRC2), is expressed in both Pax7+/Myf5⁻ stem cells and Pax7+/Myf5+ committed myogenic precursors and is required for homeostasis of the adult SC pool. Mice with conditional ablation of Ezh2 in SCs have fewer muscle postnatal Pax7+ cells and reduced muscle mass and fail to appropriately regenerate. These defects are associated with impaired SC proliferation and derepression of genes expressed in nonmuscle cell lineages. Thus, EZH2 controls self-renewal and proliferation, and maintains an appropriate transcriptional program in SCs.
authors.affiliation: Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis, Musculoskeletal, and Skin Diseases (NIAMS), National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Aster H
authors.initials: AH
authors.lastname: Juan
authors.forename: Assia
authors.initials: A
authors.lastname: Derfoul
authors.forename: Xuesong
authors.initials: X
authors.lastname: Feng
authors.forename: James G
authors.initials: JG
authors.lastname: Ryall
authors.forename: Stefania
authors.initials: S
authors.lastname: Dell'Orso
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pasut
authors.forename: Hossein
authors.initials: H
authors.lastname: Zare
authors.forename: James M
authors.initials: JM
authors.lastname: Simone
authors.forename: Michael A
authors.initials: MA
authors.lastname: Rudnicki
authors.forename: Vittorio
authors.initials: V
authors.lastname: Sartorelli
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D000071221:Enhancer of Zeste Homolog 2 Protein; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D015151:Immunoblotting; D020287:In Situ Nick-End Labeling; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000166:cytology* / Q000378:metabolism*; D051763:PAX7 Transcription Factor / Q000235:genetics / Q000378:metabolism; D063151:Polycomb Repressive Complex 2; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics*
chemical_list: D051763:PAX7 Transcription Factor; D000071221:Enhancer of Zeste Homolog 2 Protein; C498410:Ezh2 protein, mouse; D011495:Histone-Lysine N-Methyltransferase; D063151:Polycomb Repressive Complex 2