Trends in Cell Biology
Volume 15, Issue 12, December 2005, Pages 666-673
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Stem cells in postnatal myogenesis: molecular mechanisms of satellite cell quiescence, activation and replenishment

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Satellite cells are the primary stem cells in adult skeletal muscle, and are responsible for postnatal muscle growth, hypertrophy and regeneration. In mature muscle, most satellite cells are in a quiescent state, but they activate and begin proliferating in response to extrinsic signals. Following activation, a subset of satellite cell progeny returns to the quiescent state during the process of self-renewal. Here, we review recent studies of satellite cell biology and focus on the key transitions from the quiescent state to the state of proliferative activation and myogenic lineage progression and back to the quiescent state. The molecular mechanisms of these transitions are considered in the context of the biology of the satellite cell niche, changes with age, and interactions with established pathways of myogenic commitment and differentiation.

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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