Walter Lauren D, Orton Jessica L, Ntekas Ioannis, Fong Ern Hwei Hannah, Maymi Viviana I, Rudd Brian D, De Vlaminck Iwijn, Elisseeff Jennifer H, Cosgrove Benjamin D
Genetics, Genomics and Development Graduate Program, Cornell University, Ithaca, NY, USA.
Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, USA.
Nat Aging. 2024 Dec;4(12):1862-1881. doi: 10.1038/s43587-024-00756-3. Epub 2024 Nov 22.
In aging, skeletal muscle regeneration declines due to alterations in both myogenic and non-myogenic cells and their interactions. This regenerative dysfunction is not understood comprehensively or with high spatiotemporal resolution. We collected an integrated atlas of 273,923 single-cell transcriptomes and high-resolution spatial transcriptomic maps from muscles of young, old and geriatric mice (~5, 20 and 26 months old) at multiple time points following myotoxin injury. We identified eight immune cell types that displayed accelerated or delayed dynamics by age. We observed muscle stem cell states and trajectories specific to old and geriatric muscles and evaluated their association with senescence by scoring experimentally derived and curated gene signatures in both single-cell and spatial transcriptomic data. This revealed an elevation of senescent-like muscle stem cell subsets within injury zones uniquely in aged muscles. This Resource provides a holistic portrait of the altered cellular states underlying muscle regenerative decline across mouse lifespan.
在衰老过程中,骨骼肌再生能力下降,这是由于肌源性细胞和非肌源性细胞及其相互作用发生了改变。这种再生功能障碍尚未得到全面或高时空分辨率的理解。我们收集了273,923个单细胞转录组的综合图谱以及年轻、老年和老年小鼠(约5、20和26月龄)在肌毒素损伤后多个时间点的肌肉高分辨率空间转录组图谱。我们确定了八种免疫细胞类型,其动态变化随年龄增长而加速或延迟。我们观察到老年和老年肌肉特有的肌肉干细胞状态和轨迹,并通过对单细胞和空间转录组数据中实验得出和整理的基因特征进行评分,评估它们与衰老的关联。这揭示了衰老肌肉损伤区域内衰老样肌肉干细胞亚群的独特增加。该资源提供了小鼠整个生命周期中肌肉再生能力下降背后细胞状态改变的整体概况。