Notch signaling is necessary to maintain quiescence in adult muscle stem cells
| Autor: | Tom H. Cheung, Ling Liu, Christopher R. R. Bjornson, Katherine M. Steeper, Thomas A. Rando, Pinky V. Tripathi |
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| Rok vydání: | 2011 |
| Předmět: |
Transgene
Notch signaling pathway Apoptosis Mice Transgenic Biology Muscle Development Article Mice medicine Animals Cell Lineage Muscle Skeletal Cells Cultured Cell Proliferation Receptors Notch Cell growth Myogenesis Skeletal muscle PAX7 Transcription Factor Cell Biology Cell Cycle Checkpoints Cell biology Adult Stem Cells medicine.anatomical_structure Immunoglobulin J Recombination Signal Sequence-Binding Protein Molecular Medicine Stem cell Signal transduction Developmental Biology Adult stem cell Signal Transduction |
| Zdroj: | Stem cells (Dayton, Ohio). 30(2) |
| ISSN: | 1549-4918 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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