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. 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.

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Published in iScience, v. 24, issue 8, 102838.

© 2021 The Authors

This is an open access article under the CC BY-NC-ND license (https://creativecommons.org/licenses/by-nc-nd/4.0/).

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This work was supported by NIH grants from the National Institutes of Arthritis and Musculoskeletal and Skin Diseases (AR060701 to C.A.P. and J.J.M., AR071753 to K.A.M, and AR075364 to D.A.E.) and National Institute on Aging (AG049086 to C.A.P. and J.J.M. and AG063994 to K.A.M).

Related Content

All snRNA-seq datasets are uploaded to the Gene Expression Omnibus (GEO) under the accession number GSE162307 and can be downloaded from the Sequence Read Archive (SRA) under the BioProject number PRJNA681403.

1-s2.0-S2589004221008063-mmc1.pdf (323 kB)
Document S1. Figures S1 and S2 and Table S1.

1-s2.0-S2589004221008063-mmc2.xlsx (1252 kB)
Data S1. Supplemental spreadsheets file 1, related to Figures 1 and 2.

1-s2.0-S2589004221008063-mmc3.xlsx (964 kB)
Data S2. Supplemental spreadsheets file 2, related to Figures 1 and 2.

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Graphical abstract