Mechanisms of muscle stem cell function in humans

人类肌肉干细胞功能的机制

• 批准号: 327073-2011
• 负责人: Parise, Gianni
• 金额: $ 2.91万
• 依托单位: McMaster University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2013
• 资助国家: 加拿大
• 起止时间: 2013-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=526810
• 关键词: Mechanisms; muscle; stem; cell; function

Skeletal muscle accounts for over 70% of metabolically active tissue in the human body. It is responsible for the regulation of numerous bodily functions, and the loss of skeletal muscle leads to profound morbidity and dysfunction. A key element in skeletal muscle growth is the presence of muscle specific stem cells referred to as satellite cells. These cells are responsible for the growth, remodelling and repair of skeletal muscle. Moreover, skeletal muscle possesses a remarkable capacity for regeneration, entirely due to the function of satellite cells. Regrettably, we know very little about how these cells are regulated, particularly in human muscle. The importance of understanding the various processes of skeletal muscle satellite cells cannot be overstated. Skeletal muscle is a tissue integral for the maintenance of health and understanding how it grows is of benefit too all Canadians. Collectively, this proposal aims to describe specific characteristics of human satellite cells, understand how they are regulated, and determine the importance of satellite cells to human muscle growth following exercise. Specifically, we will exhaustively examine the composition of the satellite cell pool to determine if there are sub-populations of satellite cells that may possess discrete functions from other sub-populations of satellite cells. Second, we will investigate the role of a factor called angiotensin II in regulating human satellite cells. We have previously shown, in animals, that angiotensin II plays an important role in muscle repair by regulating various functions in satellite cells. We plan to extend these findings to human tissue. Finally, we will examine the potential for satellite cells in humans to induce muscle growth. Surprisingly, the extent to which satellite cells control growth in humans is unknown. The proposed experiments will significantly advance our knowledge of human satellite cell function and inform the research community as to potential targets for developing strategies for maintaining muscle mass.

骨骼肌占人体代谢活跃组织的70%以上。它负责调节许多身体功能，骨骼肌的丧失会导致严重的发病率和功能障碍。骨骼肌生长的一个关键因素是被称为卫星细胞的肌肉特异性干细胞的存在。这些细胞负责骨骼肌的生长、重塑和修复。此外，骨骼肌具有显著的再生能力，这完全是由于卫星细胞的功能。遗憾的是，我们对这些细胞是如何被调节的知之甚少，尤其是在人体肌肉中。了解骨骼肌卫星细胞的各种过程的重要性不能被夸大。骨骼肌是维持健康不可或缺的组织，了解它如何生长对所有加拿大人都有好处。总的来说，本提案旨在描述人类卫星细胞的具体特征，了解它们是如何被调节的，并确定卫星细胞对运动后人类肌肉生长的重要性。具体而言，我们将详尽地检查卫星细胞池的组成，以确定是否存在可能具有与其他卫星细胞亚群不同的功能的卫星细胞亚群。其次，我们将研究一种叫做血管紧张素II的因子在调节人类卫星细胞中的作用。我们之前在动物实验中表明，血管紧张素II通过调节卫星细胞的各种功能，在肌肉修复中起着重要作用。我们计划将这些发现扩展到人体组织。最后，我们将研究人体卫星细胞诱导肌肉生长的潜力。令人惊讶的是，卫星细胞对人体生长的控制程度尚不清楚。拟议的实验将大大提高我们对人类卫星细胞功能的认识，并告知研究界发展维持肌肉质量策略的潜在目标。