Myonuclear transcriptional dynamics in response to exercise following satellite cell depletion
Yuan Wen,
Davis A. Englund,
Bailey D. Peck,
Kevin A. Murach,
John J. McCarthy,
Charlotte A. Peterson
Affiliations
Yuan Wen
Department of Physical Therapy, College of Health Sciences, University of Kentucky, 900 S. Limestone, Lexington, KY 40536-0200, USA; Center for Muscle Biology, University of Kentucky, Lexington, KY, USA
Davis A. Englund
Department of Physical Therapy, College of Health Sciences, University of Kentucky, 900 S. Limestone, Lexington, KY 40536-0200, USA; Center for Muscle Biology, University of Kentucky, Lexington, KY, USA
Bailey D. Peck
Department of Physical Therapy, College of Health Sciences, University of Kentucky, 900 S. Limestone, Lexington, KY 40536-0200, USA; Center for Muscle Biology, University of Kentucky, Lexington, KY, USA
Kevin A. Murach
Department of Physical Therapy, College of Health Sciences, University of Kentucky, 900 S. Limestone, Lexington, KY 40536-0200, USA; Center for Muscle Biology, University of Kentucky, Lexington, KY, USA
John J. McCarthy
Center for Muscle Biology, University of Kentucky, Lexington, KY, USA; Department of Physiology, College of Medicine, University of Kentucky, Lexington, KY, USA
Charlotte A. Peterson
Department of Physical Therapy, College of Health Sciences, University of Kentucky, 900 S. Limestone, Lexington, KY 40536-0200, USA; Center for Muscle Biology, University of Kentucky, Lexington, KY, USA; Corresponding author
Summary: 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.
