Activation of Bmi1 expression as a tool to increase self-renewal of myogenic satellite cells in ageing and disease

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Adult skeletal muscle has remarkable ability to repair itself after injury as a result of its resident stem cell population, the ?satellite cells?. In the uninjured muscle these cells are in a resting state, after injury they are stimulated to begin proliferating, some will then differentiate to help repair the damaged muscle while others will return to the resting state and maintain the pool of satellite cells. However with age and in muscle diseases like Duchenne Muscular Dystrophy (DMD) the satellite cells ability to proliferate has been shown to decline and this results in degenerative changes in the muscles, leading to premature disability and even death. In other stem cell populations the ability to proliferate is regulated by the level of a polycomb group gene Bmi1. The loss of Bmi1 leads to a severely reduced proliferative ability and the overexpression of Bmi1 has been shown to keep cells proliferative. Here we plan to investigate the function of Bmi1 in regulating the biological functions of the satellite cell population. We will study the impact of gain of function of Bmi1 on the regenerative capacity of the satellite cells in vitro and in vivo. A restoration of Bmi1 levels in the satellite cells could potentially provide a mechanism for maintaining the muscle mass of aged muscle and coupled with other therapeutic techniques could be used to treat DMD patients.