Year: 2011
Type: article
Abstract: Satellite cells (SCs) are myogenic stem cells found in skeletal muscle that function to repair tissue damaged by injury or disease. SCs are quiescent at rest, although the signaling pathways required to maintain quiescence are unknown. Using a transgenic Notch reporter mouse and quantitative reverse-transcription polymerase chain reaction analysis of Notch target genes, we determined that Notch signaling is active in quiescent SCs. SC-specific deletion of recombining binding protein-Jκ (RBP-Jκ), a nuclear factor required for Notch signaling, resulted in the depletion of the SC pool and muscles that lacked any ability to regenerate in response to injury. SC depletion was not due to apoptosis. Rather, RBP-Jκ-deficient SCs spontaneously activate, fail to self-renew, and undergo terminal differentiation. Intriguingly, most of the cells differentiate without first dividing. They then fuse with adjacent myofibers, leading to the gradual disappearance of SCs from the muscle. These results demonstrate the requirement of Notch signaling for the maintenance of the quiescent state and for muscle stem cell homeostasis by the regulation of self-renewal and differentiation, processes that are all critical for normal postnatal myogenesis.
Source: Stem Cells
DOI: 10.1002/stem.773
Institutions: Stanford University, VA Palo Alto Health Care System
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
Funders: U.S. Department of Veterans Affairs, Glenn Foundation for Medical Research, Oregon Health and Science University, Johns Hopkins University, Fondation pour la Recherche Médicale, National Institutes of Health, University of California, San Diego, National Institute on Aging, National Institute of Arthritis and Musculoskeletal and Skin Diseases
OpenAlex ID: W2015185372