Abstract
Skeletal muscle comprises 30–40% of the weight of a healthy human body and is required for voluntary movements in humans. Mature skeletal muscle is formed by multinuclear cells, which are called myofibers. Formation of myofibers depends on the proliferation, differentiation, and fusion of muscle progenitor cells during development and after injury. Muscle progenitor cells are derived from muscle satellite (stem) cells (MuSCs), which reside on the surface of the myofiber but beneath the basement membrane. MuSCs play a central role in postnatal maintenance, growth, repair, and regeneration of skeletal muscle. In sedentary adult muscle, MuSCs are mitotically quiescent, but are promptly activated in response to muscle injury. Physiological and chronological aging induces MuSC aging, leading to an impaired regenerative capability. Importantly, in pathological situations, repetitive muscle injury induces early impairment of MuSCs due to stem cell aging and leads to early impairment of regeneration ability. In this review, we discuss (1) the role of MuSCs in muscle regeneration, (2) stem cell aging under physiological and pathological conditions, and (3) prospects related to clinical applications of controlling MuSCs.
Highlights
Skeletal muscle is one of the largest organs in the human body, and the weight of skeletal muscle is approximately 30–40% of the human body [1]
Skeletal muscle has an outstanding regenerative capacity that relies on muscle satellite (stem) cells (MuSCs), but this regenerative capacity after injury declines with aging [56,57,58]
To develop a therapeutic approach for skeletal muscle regeneration, it is important to understand the molecular mechanisms in how stem cells are maintained and contribute to the regeneration
Summary
Skeletal muscle is one of the largest organs in the human body, and the weight of skeletal muscle is approximately 30–40% of the human body [1]. Skeletal muscle maintains its function and size through regeneration after muscle injury. Quiescent MuSCs differentiate into mature myofibers in a stepwise fashion with serial expression of myogenic transcription factors [5,6] This differentiation program resembles the process of embryonic skeletal muscle development [5,6]. Certain rare populations of quiescent MuSCs and several types of progenies can be identified by unique expression patterns of several marker genes in combination [7] These genes are used as markers to identify the cell status, and they play roles in biological function, such as specific gene expression, proliferation, differentiation, migration, and metabolism [8]. We discuss the role of MuSCs in muscle regeneration, stem cell aging under physiological and pathological conditions, and prospects related to clinical applications of controlling MuSCs
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