华大基因研究院Miguel A. Esteban等研究人员合作绘制出衰老人类骨骼肌的多模态细胞图谱。2024年4月22日，《自然》杂志在线发表了这一最新研究成果。

研究人员绘制了人类四肢骨骼肌的单细胞/单核转录组和染色质可及性图谱，其中包括超过387000个细胞/核，这些细胞/核来自年龄在15到99岁之间、体能和虚弱程度各不相同的个体。研究人员描述了衰老过程中细胞群的变化，包括老年人中新细胞群的出现，以及与这些变化相关的细胞特异性和多细胞网络特征（转录组和表观遗传水平）。

在与遗传数据交叉比较的基础上，研究人员还确定了标志着肌少症易感性的染色质结构的关键元件。这项研究为确定骨骼肌中适合在晚年进行医疗、药物和生活方式干预的目标奠定了基础。

据了解，肌肉萎缩和功能衰退（肌肉疏松症）是体弱的常见表现，也是导致老年人发病和死亡的关键因素。破译肌肉疏松症的分子机制对了解人类衰老具有重要意义。然而，研究进展缓慢，部分原因是难以确定骨骼肌生态位异质性（其中肌纤维含量最高）的特征，也难以获得特征良好的人体样本。

附：英文原文

Title: Multimodal cell atlas of the ageing human skeletal muscle

Author: Lai, Yiwei, Ramrez-Pardo, Ignacio, Isern, Joan, An, Juan, Perdiguero, Eusebio, Serrano, Antonio L., Li, Jinxiu, Garca-Domnguez, Esther, Segals, Jessica, Guo, Pengcheng, Lukesova, Vera, Andrs, Eva, Zuo, Jing, Yuan, Yue, Liu, Chuanyu, Via, Jos, Domnech-Fernndez, Julio, Gmez-Cabrera, Mari Carmen, Song, Yancheng, Liu, Longqi, Xu, Xun, Muoz-Cnoves, Pura, Esteban, Miguel A.

Issue&Volume: 2024-04-22

Abstract: Muscle atrophy and functional decline (sarcopenia) are common manifestations of frailty and are critical contributors to morbidity and mortality in older people1. Deciphering the molecular mechanisms underlying sarcopenia has major implications for understanding human ageing2. Yet, progress has been slow, partly due to the difficulties of characterizing skeletal muscle niche heterogeneity (whereby myofibres are the most abundant) and obtaining well-characterized human samples3,4. Here we generate a single-cell/single-nucleus transcriptomic and chromatin accessibility map of human limb skeletal muscles encompassing over 387,000 cells/nuclei from individuals aged 15 to 99 years with distinct fitness and frailty levels. We describe how cell populations change during ageing, including the emergence of new populations in older people, and the cell-specific and multicellular network features (at the transcriptomic and epigenetic levels) associated with these changes. On the basis of cross-comparison with genetic data, we also identify key elements of chromatin architecture that mark susceptibility to sarcopenia. Our study provides a basis for identifying targets in the skeletal muscle that are amenable to medical, pharmacological and lifestyle interventions in late life.

DOI: 10.1038/s41586-024-07348-6

Source: https://www.nature.com/articles/s41586-024-07348-6