Polycomb EZH2 controls self-renewal and safeguards the transcriptional identity of skeletal muscle stem cells
Aster H Juan, Assia Derfoul, Xuesong Feng, James G Ryall, Stefania Dell'Orso, Alessandra Pasut, Hossein Zare, James M Simone, Michael A Rudnicki, Vittorio Sartorelli
Genes & Development | COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT | Published : 2011
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 appro..View full abstract
Awarded by NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES
We thank Mario Capecchi, David Goldhamer, and Alexander Tarakhovsky for sharing the Pax7-Cre, MyoD-Cre, and Ezh2<SUP>fl/fl</SUP> animals, respectively. Fabio Rossi provided advice with the FACS experiments, Jeffrey Lay helped with cell sorting, and Gustavo Gutierrez-Cruz assisted with animal genotyping. Members of the NIAMS Laboratory Animal Care and Use Section and NIAMS Light Imaging Section are kindly acknowledged. J.G.R. was supported by an Overseas Biomedical Research Fellowship from the NH and MRC (Australia). This work was supported in part by the Intramural Research Program of the National Institute of Arthritis, Musculoskeletal, and Skin Diseases of the National Institutes of Health.