Mechanisms of muscle stem cell function in humans

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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.