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02 / 10 / 2017

What role has the stem cell niche for skeletal muscle stem cell function? (MAYER_U18DTP1)

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Men and women lose 50% of their skeletal muscle mass in later life through a process called age-related sarcopenia, characterised by a combined loss of muscle mass, endurance and strength. This results in progressive loss in mobility eventually leading to loss of independence in old age. Because of the changing demographics in the UK, where the population aged 80 years and older is predicted to double over the next 20 years, there is a need to study mechanisms of age-related sarcopenia, which lead to intervention strategies designed to reduce muscle loss. Satellite cells (SCs) are the resident skeletal muscle stem cells and the main contributors to muscle repair, either after injury or in muscle wasting diseases. SCs are quiescent myogenic stem cells, which become rapidly activated upon injury. The SC pool size and its proliferative capacity diminish with age, eventually leading to defective muscle maintenance and repair. SCs are embedded in a specialised niche between the basement membrane and the plasma membrane of the muscle fibre. However, little is known what role this niche plays in regulating activation and self-renewal of SCs, or age-related alterations that may contribute to muscle loss. We will use in vivo and in vivo experiments to define the role of two integrins, integrin α7 and α5 for SC behaviour, as well as ex vivo single fibre assays and investigate the cellular processes that are perturbed when these transmembrane receptors of SCs are absent.