Early satellite cell communication creates a permissive environment for long-term muscle growth
Kevin A. Murach,
Bailey D. Peck,
Robert A. Policastro,
Ivan J. Vechetti,
Douglas W. Van Pelt,
Cory M. Dungan,
Lance T. Denes,
Xu Fu,
Camille R. Brightwell,
Gabriel E. Zentner,
Esther E. Dupont-Versteegden,
Christopher I. Richards,
Jeramiah J. Smith,
Christopher S. Fry,
John J. McCarthy,
Charlotte A. Peterson
Affiliations
Kevin A. Murach
The Center for Muscle Biology, University of Kentucky, Lexington, KY 40536, USA; Department of Physical Therapy, College of Health Sciences, University of Kentucky, Lexington, KY 40536, USA
Bailey D. Peck
The Center for Muscle Biology, University of Kentucky, Lexington, KY 40536, USA; Department of Physical Therapy, College of Health Sciences, University of Kentucky, Lexington, KY 40536, USA
Robert A. Policastro
Department of Biology, College of Arts and Sciences, University of Indiana, Bloomington, IN 47405, USA
Ivan J. Vechetti
The Center for Muscle Biology, University of Kentucky, Lexington, KY 40536, USA; Department of Physiology, College of Medicine, University of Kentucky, Lexington, KY 40536, USA; Department of Nutrition and Health Sciences, College of Education and Human Sciences, University of Nebraska, Lincoln, NE 68588, USA
Douglas W. Van Pelt
The Center for Muscle Biology, University of Kentucky, Lexington, KY 40536, USA; Department of Physical Therapy, College of Health Sciences, University of Kentucky, Lexington, KY 40536, USA
Cory M. Dungan
The Center for Muscle Biology, University of Kentucky, Lexington, KY 40536, USA; Department of Physical Therapy, College of Health Sciences, University of Kentucky, Lexington, KY 40536, USA
Lance T. Denes
Department of Molecular Genetics and Microbiology, Center for Neurogenetics, University of Florida, Gainesville, FL 32611, USA
Xu Fu
Department of Chemistry, College of Arts and Sciences, University of Kentucky, Lexington, KY 40536, USA
Camille R. Brightwell
The Center for Muscle Biology, University of Kentucky, Lexington, KY 40536, USA; Department of Athletic Training, College of Health Sciences, University of Kentucky, Lexington, KY 40536, USA
Gabriel E. Zentner
Department of Biology, College of Arts and Sciences, University of Indiana, Bloomington, IN 47405, USA
Esther E. Dupont-Versteegden
The Center for Muscle Biology, University of Kentucky, Lexington, KY 40536, USA; Department of Physical Therapy, College of Health Sciences, University of Kentucky, Lexington, KY 40536, USA
Christopher I. Richards
Department of Chemistry, College of Arts and Sciences, University of Kentucky, Lexington, KY 40536, USA
Jeramiah J. Smith
Department of Biology, College of Arts and Sciences, University of Kentucky, Lexington, KY 40506, USA
Christopher S. Fry
The Center for Muscle Biology, University of Kentucky, Lexington, KY 40536, USA; Department of Athletic Training, College of Health Sciences, University of Kentucky, Lexington, KY 40536, USA
John J. McCarthy
The Center for Muscle Biology, University of Kentucky, Lexington, KY 40536, USA; Department of Physiology, College of Medicine, University of Kentucky, Lexington, KY 40536, USA; Corresponding author
Charlotte A. Peterson
The Center for Muscle Biology, University of Kentucky, Lexington, KY 40536, USA; Department of Physical Therapy, College of Health Sciences, University of Kentucky, Lexington, KY 40536, USA; Department of Physiology, College of Medicine, University of Kentucky, Lexington, KY 40536, USA; Corresponding author
Summary: Using in vivo muscle stem cell (satellite cell)-specific extracellular vesicle (EV) tracking, satellite cell depletion, in vitro cell culture, and single-cell RNA sequencing, we show satellite cells communicate with other cells in skeletal muscle during mechanical overload. Early satellite cell EV communication primes the muscle milieu for proper long-term extracellular matrix (ECM) deposition and is sufficient to support sustained hypertrophy in adult mice, even in the absence of fusion to muscle fibers. Satellite cells modulate chemokine gene expression across cell types within the first few days of loading, and EV delivery of miR-206 to fibrogenic cells represses Wisp1 expression required for appropriate ECM remodeling. Late-stage communication from myogenic cells during loading is widespread but may be targeted toward endothelial cells. Satellite cells coordinate adaptation by influencing the phenotype of recipient cells, which extends our understanding of their role in muscle adaptation beyond regeneration and myonuclear donation.
