Abstract
Adult skeletal muscle possesses extraordinary regeneration capacities. After muscle injury or exercise, large numbers of newly formed muscle fibers are generated within a week as a result of expansion and differentiation of a self-renewing pool of muscle stem cells termed muscle satellite cells. Normally, satellite cells are mitotically quiescent and reside beneath the basal lamina of muscle fibers. Upon regeneration, satellite cells are activated, and give rise to daughter myogenic precursor cells. After several rounds of proliferation, these myogenic precursor cells contribute to the formation of new muscle fibers. During cell division, a minor population of myogenic precursor cells returns to quiescent satellite cells as a self-renewal process. Currently, accumulating evidence has revealed the essential roles of satellite cells in muscle regeneration and the regulatory mechanisms, while it still remains to be elucidated how satellite cell self-renewal is molecularly regulated and how satellite cells are important in aging and diseased muscle. The number of satellite cells is decreased due to the changing niche during ageing, resulting in attenuation of muscle regeneration capacity. Additionally, in Duchenne muscular dystrophy (DMD) patients, the loss of satellite cell regenerative capacity and decreased satellite cell number due to continuous needs for satellite cells lead to progressive muscle weakness with chronic degeneration. Thus, it is necessary to replenish muscle satellite cells continuously. This review outlines recent findings regarding satellite cell heterogeneity, asymmetric division and molecular mechanisms in satellite cell self-renewal which is crucial for maintenance of satellite cells as a muscle stem cell pool throughout life. In addition, we discuss roles in the stem cell niche for satellite cell maintenance, as well as related cell therapies for approaching treatment of DMD.
Highlights
Skeletal muscle is the most abundant tissue in the mammalian body accounting for approximately 40% of body weight, and is composed of multinucleated fibers that contract to generate force and movement
Following a cardiotoxin-induced skeletal muscle injury, the Pax7 KO mutant displayed significantly reduced muscle regeneration capacity. These results strongly indicate that Pax7 is essential for normal skeletal muscle growth and regeneration through the maintenance and regulation of muscle satellite cells (Oustanina et al, 2004; Kuang et al, 2006)
The absence of the Spry1 gene has shown a reduction in satellite cell number after muscle regeneration, suggesting that Spoutry-1 is required for the return of myogenic precursor cells to a quiescent state through inhibition of Fibroblast growth factors (FGF) signaling and replenishment of the satellite cell pool during muscle regeneration (Shea et al, 2010)
Summary
Skeletal muscle is the most abundant tissue in the mammalian body accounting for approximately 40% of body weight, and is composed of multinucleated fibers that contract to generate force and movement. These observations strongly suggested that down-regulation of MyoD expression is a key event for the satellite cell self-renewal process, and identification of genes and factors that repress MyoD expression may be important for the clarification of satellite cell pool maintenance mechanisms.
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