GSE162307
Satellite cell depletion results in a cryptic subpopulation of myonuclei in response to exercise
Skeletal muscle is composed of post-mitotic myofibers that form a syncytium containing hundreds of myonuclei. Using a progressive exercise training model in the mouse and single nucleus RNA-sequencing (snRNA-seq) for high resolution characterization of myonuclear transcription, we show myonuclear functional specialization in muscle from sedentary mice that is altered by 4 weeks of exercise training. Furthermore, in response to exercise, snRNA-seq reveals that resident muscle stem cells, satellite cells, were activated, but demonstrated limited lineage progression while contributing to muscle adaption. In the absence of satellite cells, trajectory analysis predicts the emergence of cryptic myonuclei that appear to lose their canonical identity. These data illustrate how myonuclear adaptation to exercise may be disrupted under conditions satellite cell compromise. Overall design: We used a genetic mouse model to fluorescently label and purify myonuclei from skeleletal muscle to investigate single-myonuclear transcriptomes using single-nucleus RNA-sequencing. Additionally, we used a translatable model of exercise training in conjunction with a mouse model of inducible satellite cell (skeletal muscle precursor cells) ablation to study single-nuclear transcriptomic changes after 4-weeks of exercise training at 4 and 24 hours after the last bout of exercise.