摘要:SummarySkeletal 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. After 4 weeks of exercise training, snRNA-seq reveals that resident muscle stem cells, or satellite cells, are activated with acute exercise but demonstrate limited lineage progression while contributing to muscle adaptation. In the absence of satellite cells, a portion of nuclei demonstrates divergent transcriptional dynamics associated with mixed-fate identities compared with satellite cell replete muscles. These data provide a compendium of information about how satellite cells influence myonuclear transcription in response to exercise.Graphical abstractDisplay OmittedHighlights•Single nucleus RNA-sequencing, trajectory inference, and entropy analyses•Genetic depletion of satellite cells before exercise training in adult mice•Dysregulated nuclei arise 24 h after last exercise bout when without satellite cells•Satellite cell depletion alters myonuclear transcription during growth and adaptationBiological sciences; Stem cells research; Transcriptomics