The role of integrins in muscle stem cell function

整合素在肌肉干细胞功能中的作用

• 批准号: 2589577
• 金额: --
• 依托单位: University of East Anglia
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2589577
• 关键词: role; integrins; muscle; stem; cell

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 frailty and 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 can lead to intervention strategies designed to reduce muscle loss.Satellite cells are the resident skeletal muscle stem cells and the main contributors to muscle repair, either after injury or in muscle wasting diseases. Satellite cells are quiescent myogenic stem cells, which become rapidly activated upon injury. The satellite cell pool and its proliferative capacity diminish with age, eventually leading to defective muscle maintenance and repair. Satellite cells 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.The project will use in vivo and in vitro experiments to define the role of two integrins, integrin a7 and a5, for satellite cell behaviour, as well as ex vivo single muscle fibre assays and investigate the cellular processes that are perturbed when these transmembrane receptors expressed by satellite cells are absent.

男性和女性在晚年会通过一种称为“年龄相关性肌肉减少症”的过程损失 50% 的骨骼肌质量，其特征是肌肉质量、耐力和力量的综合损失。这导致行动能力逐渐丧失，最终导致老年时身体虚弱和失去独立性。由于英国人口结构的变化，预计未来 20 年内 80 岁及以上的人口将增加一倍，因此有必要研究与年龄相关的肌肉减少症的机制，从而制定旨在减少肌肉损失的干预策略。卫星细胞是常驻骨骼肌干细胞，是受伤后或肌肉消耗性疾病中肌肉修复的主要贡献者。卫星细胞是静止的肌源干细胞，在受伤时会迅速激活。卫星细胞池及其增殖能力随着年龄的增长而减弱，最终导致肌肉维护和修复缺陷。卫星细胞嵌入肌纤维的基底膜和质膜之间的特殊生态位中。然而，很少有人知道这个生态位在调节 SC 的激活和自我更新或可能导致肌肉损失的年龄相关改变中发挥什么作用。该项目将使用体内和体外实验来定义两个整合素（整合素 a7 和 a5）对于卫星细胞行为的作用，以及离体单肌纤维测定，并研究当这些整合素发生变化时受到干扰的细胞过程。 卫星细胞表达的跨膜受体不存在。