Notch Signaling Is Necessary to Maintain Quiescence in Adult Muscle Stem Cells
Top Cited Papers
- 18 January 2012
- journal article
- tissue specific-stem-cells
- Published by Oxford University Press (OUP) in The International Journal of Cell Cloning
- Vol. 30 (2), 232-242
- https://doi.org/10.1002/stem.773
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. Disclosure of potential conflicts of interest is found at the end of this article.Keywords
Funding Information
- Glenn Foundation for Medical Research and by grants from the NIH (P01 AG036695, R37 AG23806, R01 AR056849)
- NIH Director's Pioneer Award) and the Department of Veterans Affairs
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