Polycomb EZH2 controls self-renewal and safeguards the transcriptional identity of skeletal muscle stem cells
- Aster H. Juan1,
- Assia Derfoul1,4,
- Xuesong Feng1,4,
- James G. Ryall1,4,
- Stefania Dell'Orso1,4,
- Alessandra Pasut2,4,
- Hossein Zare1,
- James M. Simone3,
- Michael A. Rudnicki2 and
- Vittorio Sartorelli1,5
- 1Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis, Musculoskeletal, and Skin Diseases (NIAMS), National Institutes of Health, Bethesda, Maryland 20892, USA;
- 2The Sprott Centre for Stem Cell Research, Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Ontario K1H8L6, Canada;
- 3Flow Cytometry Section, NIAMS, National Institutes of Health, Bethesda, Maryland 20892, USA
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↵4 These authors contributed equally to this work.
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.
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Footnotes
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↵5 Corresponding author.
E-MAIL sartorev{at}mail.nih.gov; FAX (301) 480-9699.
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Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.2027911.
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Supplemental material is available for this article.
- Received January 1, 2011.
- Accepted March 3, 2011.
