Abstract
Emerging evidence suggests that metabolites are important regulators of skeletal muscle stem cell (MuSC) function and fate. While highly proliferative in early life, MuSCs reside in adult skeletal muscle tissue in a quiescent and metabolically depressed state, but are critical for the homeostatic maintenance and regenerative response of the tissue to damage. It is well established that metabolic activity in MuSC changes with their functional activation, but the spatiotemporal links between physiological metabolism and stem cell metabolism require explicit delineation. The quiescent MuSC is defined by a specific metabolic state, which is controlled by intrinsic and extrinsic factors during physiological and pathological tissue dynamics. However, the extent of tissue and organismal level changes driven by alteration in metabolic state of quiescent MuSC is currently not well defined. In addition to their role as biosynthetic precursors and signaling molecules, metabolites are key regulators of epigenetic mechanisms. Emerging evidence points to metabolic control of epigenetic mechanisms in MuSC and their impact on muscle regenerative capacity. In this review, we explore the links between cell-intrinsic, tissue level, and systemic metabolic state in the context of MuSC metabolic state, quiescence, and tissue homeostasis to highlight unanswered questions.
Highlights
Nutrition is a prerequisite for energy production, homeostasis, and growth
Three major factors define the systemic metabolic state of an organism: (1) caloric value of the food consumed, (2) basal metabolic rate of the body coupled to physical activity, and (3) pathological condition(s)
The quest is to understand the role of metabolism in development, disease, and regeneration
Summary
Nutrition is a prerequisite for energy production, homeostasis, and growth. In mammals, prenatal development is largely dependent on the maternal nutritional status, conveyed to the fetus via the placenta. Associated with myofibers in adult muscle is a rare population of muscle stem cells (MuSCs) called satellite cells, which are injury-responsive and can robustly repair or replace damaged myofibers. When considering the metabolic state of muscle tissue, it is important to factor in the requirements and responses of MuSCs as distinct from the differentiated myofibers: a minor component of the tissue as a whole, they are essential for maintenance of muscle tissue (see Box 2 for a brief overview of major metabolites and metabolic pathways). We assess the available evidence that provides links between systemic, tissue, and stem cell metabolism in the context of skeletal muscle and outline the current understanding of metabolic regulation of MuSC epigenetic state. We highlight open questions that constitute important avenues of future research with potential translational significance
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