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Stem cells in adult tissues, like pluripotent stem cells possess the capacity to self-renew and differentiate into multiple mature cell types. In a process that is less well-defined, stem cells replenish their pool integrating cues from the niche and intracellular signaling pathways, thereby protecting the tissue from degeneration and cancerous conditions. My specific interests lie in trying to understand the molecular mechanisms that govern stem cell self-renewal, using skeletal muscle as a model system. Regeneration in skeletal muscle is accomplished primarily by a geographically defined population of cells called “satellite cells”. We have discovered a role for the longevity gene and forkhead transcription factor, Foxo3, in satellite cells, that is essential for their return to quiescence and for regeneration in muscle that has undergone repeated injuries. More detailed analysis revealed that a FOXO3-Notch axis is important for satellite cell self-renewal by promoting the re-acquisition of the quiescent state during the self-renewal process. Another important parameter of stem cell functionality is the ability of adult stem cells to faithfully divide and give rise to committed progenitors. However, transdifferentiating stem cells contribute to pathological conditions such as fibrosis or adipogenesis in the context of disease and ageing. Using a dystrophic model, we have tried to address the contribution of satellite cells to fibrosis and the molecular mechanisms involved in this process. |