Résumé :
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Skeletal muscle tissue is prone to damage from acute physical trauma such as sport injuries as well as from daily wear and tear: this is managed by its tremendous capacity to repair itself. Cell transplantation and lineage tracing studies have demonstrated that Pax7 expressing satellite cells can repeatedly repair damaged muscle tissue after several bouts of acute injury, providing evidence that they are muscle stem cells. Lineage tracing studies by chick/quail chimeras and by the constitutive Cre recombination system in mice have demonstrated a somitic origin for Pax7 expressing satellite cells emerging in late embryogenesis. However, any possible differences in the developmental potential of Pax7-expressing cell populations at distinct developmental time points could not be ascertained due to the cumulative marking of all descendants of cells that express Cre at one time. Using temporally controlled lineage tracing of Pax7-descendant cells from different embryonic stages, we demonstrate that adult satellite cells have an embryonic origin. Moreover, while Pax7 expressing cells give rise to several different lineages at earlier embryonic stages (e.g. embryonic day 9.5) including the dorsal dermis, brown adipose tissue and trunk muscles, at later stages (e.g. embryonic day 12.5) their lineage becomes restricted to the skeletal muscle fate including muscle fibers and satellite cells in the limb. We further demonstrate that such embryonically derived satellite cells serve as a source of myogenic stem cells for injury-induced muscle regeneration. However, since each muscle fiber forms as a syncytium, it is still unresolved if Pax7 expressing satellite cells are the only source for these new myofibers after acute injury. Moreover, many studies have demonstrated that stem cells of other origins can contribute to regenerative myogenesis but their normal physiological relevance to muscle repair is entirely unknown. To test whether there is any significant contribution to muscle regeneration from non-Pax7 expressing cells, we engineered genetic ablation of Pax7-positive cells and assayed for regenerative myogenesis induced by acute injury. Unexpectedly, we find that such elimination of Pax7-positive cells completely blocks regenerative myogenesis either following injury to the tibialis anterior muscle or after transplantation of extensor digitorum longus muscles into nude mice. As Pax7 is specifically expressed in satellite cells, we conclude that they are the sole source of myogenic stem cells for acute injury-induced muscle regeneration.
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