The role of stem and progenitor cell populations in skeletal muscle homeostasis, repair and regeneration. (360G-Wellcome-084241_Z_07_Z)

Skeletal muscle repair and regeneration requires the mobilization, proliferation and differentiation of progenitor cell populations. We have developed in vivo mouse models to assay the capacity of satellite cells and other progenitor cells to contribute to skeletal muscle regeneration and to repopulate the satellite cell compartment with functional stem cells. We have shown that a sub-population of the satellite cell pool are stem cells, that have the capacity both to regenerate skeletal muscle and to self-renew and repopulate the satellite cell pool the satellite stem cell (SSC). However, up till now we have not been able to identify and separate SSC from non-stem satellite cells. We now propose to identify novel markers of SSC to allow us to determine which sub-population of satellite cells is SSC. Identification will be reliant on proliferative and metabolic status, and unique cell surface phenotypic markers. We will use these markers to fractionate and purify SSC from dystrop hic and aged muscles and investigate the degree to which the hostile environment within aged or dystrophic muscle is capable of compromising their abundance or their biological function.