Trends in Cell Biology
Stem cells in postnatal myogenesis: molecular mechanisms of satellite cell quiescence, activation and replenishment
Section snippets
The quiescent state
Satellite cells as a population are primarily quiescent, dividing very infrequently under normal conditions in the adult. Several lines of evidence suggest that quiescence is not merely an inactive basal state, but rather is a state under active transcriptional control [11]. The study of satellite cell quiescence has been difficult because they are a very small population of cells in vivo and because the process of isolating satellite cells invariably leads to their activation. In this respect,
Satellite cell activation and myogenic lineage progression
The activation of satellite cells is a multistep process. Ultimately, the activating signals received by quiescent satellite cells lead to the transition from G0 to G1 phase of the cell cycle, i.e. exit from the quiescent state. Once the satellite cells have entered into their first cell cycle, they proceed through a highly proliferative intermediate progenitor stage (analogous to the ‘transit amplifying’ phase of stem cells in the skin, gut and other tissues 33, 34) characterized by high
The replenishment of satellite cells and the return to quiescence
The number of satellite cells in an adult muscle remains relatively constant through repeated bouts of injury and regeneration [6], thus assuring a sufficient reserve for future needs. It has long been assumed that replenishment comes from the ability of satellite cells to self-renew [47]. However, until recently, direct evidence has been lacking. Satellite cells on isolated myofibers activate and adopt divergent fates, one of which is consistent with a return to quiescence [48]. However, in a
Concluding remarks
In summary, the molecular mechanisms that control satellite cell quiescence, activation and self-renewal are not well understood, but patterns of gene expression, alternative splicing of transcripts, and protein levels that coincide with these different states and transitions, are providing the framework for that understanding. It is clear that genetic studies using conditional and inducible changes, either down-regulation or enhanced expression, in specific pathways will be necessary to
Acknowledgements
We thank Andrew Brack, Valerie Renault, Suchitra Gopinath, Sindhu Subramanian and Grace Pavlath for critical reading of the manuscript. The authors would like to acknowledge the support of the Council for Scientific and Industrial Research, the Department of Biotechnology, the Indian Council for Medical Research and the Wellcome Trust (J.D.) and the NIH, the Ellison Medical Foundation, and the Department of Veterans Affairs (T.A.R.).
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