Maintaining the regenerative compartment of adult skeletal muscle

Beauchamp, J.R.; Zammit, P.S.; Nagata, Y.; Golding, J. and Partridge, T.A. (2005). Maintaining the regenerative compartment of adult skeletal muscle. In: Congress of Myology, 09-13 May 2005, Nantes, France.



Skeletal muscle is predominantly composed of highly specialised contractile myofibres, each maintained by hundreds of postmitotic myonuclei. Throughout adult life, new myonuclei are required to meet the persistent demands of myofibre turnover, growth and repair. These are provided by the differentiation of myoblasts, generated from the satellite cells that reside between the plasmalemma and surrounding basal lamina of mature myofibres. Although the progression from satellite cell to myonucleus is well established, the mechanisms by which an effective regenerative compartment is maintained remain controversial. Indeed, it has been suggested that satellite cells are “arrested” myogenic precursors that are replenished from other stem cells located within the muscle interstitium and/or from outside the tissue. Using an isolated myofibre culture system to investigate early events of satellite cell activation, proliferation and differentiation, we have shown that in the context of the sublaminal niche, satellite cell progeny can adopt divergent fates. In this model system, quiescent Pax7+ve/MyoD-ve satellite cells are synchronously activated to produce a homogenous Pax7+ve/MyoD+ve population. These cells proliferate and generate clusters of myoblasts, most of which become Pax7-ve/myogenin+ve and are fated to undergo terminal differentiation. Significantly, some cells within the clusters maintain expression of Pax7 and down regulate MyoD, apparently returning to a state of quiescence comparable to that of the initial Pax7+ve/MyoD-ve population. Our observations demonstrate that satellite cells have the potential to generate both myonuclei and new satellite cells and suggest that the alternate fate decisions may be extrinsically imposed on a homogeneous population. Most importantly, these findings suggest that the satellite cell pool may be maintained by self-renewal and does not necessarily require a contribution from elsewhere.

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