Epigenetic determinants of muscle stem cell quiescence and chronological aging

Skeletal muscle is a post-mitotic tissue that exhibits an extremely low turnover in the absence of disease or injury. At the same time, muscle possesses remarkable regenerative capacity mediated by satellite cells (SCs) that reside in close association with individual myofibers, underneath the fibers basal lamina. Consistent with the low turnover of the muscle, SCs in adult animals are mitotically quiescent and therefore provide an excellent model to study stem cell quiescence. As an organism grows older, the resident stem cells are exposed to a deteriorating environment and experience chronological aging. In stem cells with high turnover, the effects of chronological aging are superimposed upon the effects of the replicative aging that results from DNA replication and cell division. On the contrary, SCs experience minimal replicative aging due to their low turnover. They are thus a good model to study the consequence of chronological aging of quiescent stem cells. We performed microarray analysis of quiescent and activated SCs from both young and aged mice to understand the global gene expression profile underlying stem cell properties such as quiecence and self-renewal, and to understand how the transcriptome of a quiescent stem cell pouplation changes with age.

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Liu L, Cheung TH, Charville GW, Hurgo BM, Leavitt T, Shih J, Brunet A, Rando TA