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

激活 Bmi1 表达作为增加衰老和疾病中肌源卫星细胞自我更新的工具

• 批准号: G0802546/1
• 负责人: Silvia Marino
• 金额: $ 53.58万
• 依托单位: Queen Mary University of London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0802546%2F1
• 关键词: Activation; Bmi1; expression; tool; increase

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.

成人骨骼肌由于其固有的干细胞群，在损伤后具有显著的自我修复能力。卫星细胞？在未受伤的肌肉中，这些细胞处于静息状态，在受伤后，它们被刺激开始增殖，一些细胞然后分化以帮助修复受损的肌肉，而另一些细胞将返回静息状态并维持卫星细胞池。然而，随着年龄的增长和肌肉疾病，如杜氏肌营养不良症（DMD），卫星细胞增殖的能力已经被证明下降，这导致肌肉的退行性变化，导致过早残疾甚至死亡。在其他干细胞群体中，增殖能力受polycomb组基因Bmi 1的水平调节。Bmi 1的缺失导致增殖能力严重降低，并且Bmi 1的过表达已显示出保持细胞增殖。在这里，我们计划研究Bmi 1在调节卫星细胞群体的生物学功能中的功能。我们将在体外和体内研究Bmi 1功能获得对卫星细胞再生能力的影响。卫星细胞中Bmi1水平的恢复可能提供一种维持老年肌肉质量的机制，并与其他治疗技术相结合，可用于治疗DMD患者。