Final Report Summary - STEMDNAFATE (Genetic and Epigenetic Regulation of Stem Cell Fate)
Although it is clear that stem cells play crucial roles in establishing and repairing tissues, our knowledge of their fundamental properties, how they assure organogenesis and effect regeneration in distinct physiological contexts remains limited. A major challenge in stem cell biology is investigating these cells in their natural state in vivo and duplicating these conditions in an ex vivo microenvironement. We investigated several features of skeletal muscle stem cells and provided critical information on how they interact with their niche to remain quiescent, become mobilized to effect tissue repair, and self-renew. These studies involved linking signaling pathways with key intracellular functions to provide information on how the extracellular milieu and intracellular responses safeguard this population. For example, we identified several pathways that regulate the quiescent to activation state, as well as their migration. By using artificially designed niches in a dish, we replicated conditions where the frequency of symmetric and asymmetric cell fate decisions can be modulated. These and other studies on their metabolic profiles, and directly filming stem cell behaviours in the tissue, have provided important insights into muscle stem cell function during growth, regeneration and ageing.