Cell atlas of the ageing human skeletal muscle - Asian RNA

Muscle atrophy and frailty are common manifestations of sarcopenia and are critical contributors to morbidity and mortality in the elderly. Deciphering the underlying molecular mechanisms of sarcopenia has major implications for understanding human ageing, yet progress has been slow, in part due to the complexity of characterizing skeletal muscle niche heterogeneity (with myofibres being more abundant) and the difficulty of accessing well-characterized human samples. Here, we have generated a single-cell/single-nucleus transcriptomic and chromatin accessibility map of human limb skeletal muscles encompassing over 387,000 cells/nuclei from individuals ranging from 15 to 99 years of age with distinct fitness and frailty levels. We describe i) the changes in cell populations during distinct ages, including the emergence of new ones in the elderly, and ii) the cell-specific and multicellular network features (at the transcriptomic and epigenetic levels) that are associated with these changes. Based on cross-comparison with genetic data, we also identify key elements of chromatin architecture marking susceptibility to sarcopenia. Our study provides the basis for the identification of novel targets in the skeletal muscle amenable to medical, pharmacological and lifestyle interventions in late life.

肌肉萎缩与虚弱是肌少症（sarcopenia）的常见临床表现，同时也是老年人群发病与死亡的关键促成因素。解析肌少症潜在的分子机制，对理解人类衰老进程具有重要意义，但相关研究进展缓慢，部分原因在于骨骼肌微环境（skeletal muscle niche）异质性的表征难度较高（其中肌纤维占比更高），且难以获取经过充分表征的人类样本。本研究针对人类肢体骨骼肌构建了单细胞/单细胞核转录组（single-cell/single-nucleus transcriptomic）与染色质可及性（chromatin accessibility）图谱，涵盖来自15至99岁、健康水平与虚弱程度各异的个体的逾38.7万个细胞/细胞核。本研究阐明了：①不同年龄阶段的细胞群体变化规律，包括老年群体中新兴细胞群的出现；②与上述变化相关的细胞特异性及多细胞网络特征（涵盖转录组与表观遗传层面）。通过与遗传学数据的交叉比对，本研究还鉴定出标记肌少症易感性的关键染色质结构元件。本研究为识别可用于老年阶段医学、药物及生活方式干预的骨骼肌新型靶点提供了重要基础。

搜集汇总

背景与挑战

背景概述

该数据集提供了亚洲人衰老骨骼肌的单细胞/单核转录组和染色质可及性图谱，涵盖了广泛年龄段的个体，旨在揭示骨骼肌衰老的分子机制和细胞变化。数据规模庞大，包含387,000个细胞/核，适用于研究骨骼肌衰老的医学、药理学和生活方式干预目标。