Early satellite cell communication creates a permissive environment for long-term muscle growth

Authors

Kevin A. Murach, University of Kentucky
Bailey D. Peck, University of Kentucky
Robert A. Policastro, University of Indiana
Ivan J. Vechetti, University of KentuckyFollow
Douglas W. Van Pelt, University of Kentucky
Cory M. Dungan, University of Kentucky
Lance T. Denes, University of Flordia
Xu Fu, University of Kentucky
Camille R. Brightwell, University of Kentucky
Gabriel E. Zentner, University of Indiana
Esther E. Dupont-Versteegden, University of Kentucky
Christopher I. Richards, University of Kentucky
Jeramiah J. Smith, University of Kentucky
Christopher S. Fry, University of Kentucky
John J. McCarthy, University of Kentucky
Charlotte A. Peterson, University of Kentucky

Document Type

Article

Date of this Version

4-23-2021

Comments

OPEN ACCESS CC BY-NC-ND

Abstract

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.