4.7 Article

Myonuclear transcriptional dynamics in response to exercise following satellite cell depletion

Journal

ISCIENCE
Volume 24, Issue 8, Pages -

Publisher

CELL PRESS
DOI: 10.1016/j.isci.2021.102838

Keywords

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Funding

  1. NIH grants from the National Institutes of Arthritis and Musculoskeletal and Skin Diseases [AR060701, AR071753, AR075364]
  2. National Institute on Aging [AG049086, AG063994]

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The study revealed that satellite cells in muscle are activated during acute exercise, but show limited lineage progression during muscle adaptation. Nuclei without satellite cells demonstrate divergent transcriptional dynamics compared to muscles with sufficient satellite cells.
Skeletal muscle is composed of post-mitotic myofibers that forma 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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