Single-cell sequencing deconvolutes cellular responses to exercise in human skeletal muscle. Single-cell sequencing deconvolutes cellular responses to exercise in human skeletal muscle

Regular physical activity is a key concept associated with a variety of health-related outcomes and successful ageing. While many of the beneficial effects of physical activity are undisputed, much of the adaptive mechanisms that lead to these benefits are not yet known. The skeletal muscle is a key contributor to physical performance and is also the target organ for many of the adaptive processes associated with exercise. Skeletal muscle is highly plastic, and changes in physical activity lead to a plethora of adaptive processes that, when repeated over time, result in structural and functional adaptations. Here we use single cell sequencing in humans to outline the effects of physical activity on cellular composition and cell type-specific processes in skeletal muscle. We show that myogenic cells in human skeletal muscle can be divided into three groups characterized by different degrees of cell maturation, and that exercise stimulates subpopulation of undifferentiated stem/progenitor myogenic cells to mature toward slow- or fast-twitch fibers. The cell type-specific adaptive mechanisms induced by exercise presented here contribute to the understanding of the skeletal muscle adaptations triggered by physical activity and may ultimately have implications for physiological and pathological processes affecting skeletal muscle, such as sarcopenia, cachexia, and glucose homeostasis. Overall design: The mononuclear cells were isolated from skeletal muscle before and after exercise from three healthy individuals and subjected to single-cell sequencing.

规律性体力活动是与多种健康结局及成功衰老密切相关的核心概念。尽管体力活动的诸多有益效应已得到学界公认，但其介导此类益处的诸多适应性机制仍未完全阐明。骨骼肌是体能表现的核心贡献器官，同时也是与运动相关的多数适应性生理过程的靶器官。骨骼肌具有高度可塑性，体力活动水平的改变会引发大量适应性进程，随时间反复积累后可促成结构与功能层面的适应性重塑。本研究通过人类单细胞测序技术，系统阐明了体力活动对骨骼肌细胞组成及细胞类型特异性生理过程的影响。研究证实，人类骨骼肌中的肌源性细胞可依据细胞成熟度划分为三类；运动可促进未分化的干细胞/祖细胞样肌源性细胞亚群向慢肌纤维或快肌纤维方向成熟分化。本研究揭示的运动诱导的细胞类型特异性适应性机制，有助于深化对体力活动触发的骨骼肌适应性改变的理解，最终可为影响骨骼肌的生理与病理过程（如肌少症、恶病质及葡萄糖稳态失衡）提供潜在的理论参考与干预思路。实验设计：本研究从3名健康个体的骨骼肌中，分别采集运动前后的单核细胞并进行单细胞测序。