Depletion of skeletal muscle satellite cells attenuates pathology in muscular dystrophy

Justin G. Boyer, Jiuzhou Huo, Sarah Han, Julian R. Havens, Vikram Prasad, Brian L. Lin, David A. Kass, Taejeong Song, Sakthivel Sadayappan, Ramzi J. Khairallah, Christopher W. Ward and Jeffery D. Molkentin ()
Additional contact information
Justin G. Boyer: Cincinnati Children’s Hospital Medical Center
Jiuzhou Huo: Cincinnati Children’s Hospital Medical Center
Sarah Han: Cincinnati Children’s Hospital Medical Center
Julian R. Havens: Cincinnati Children’s Hospital Medical Center
Vikram Prasad: Cincinnati Children’s Hospital Medical Center
Brian L. Lin: Johns Hopkins Medical Institutions
David A. Kass: Johns Hopkins Medical Institutions
Taejeong Song: University of Cincinnati
Sakthivel Sadayappan: University of Cincinnati
Ramzi J. Khairallah: Myologica, LLC
Christopher W. Ward: University of Maryland School of Medicine
Jeffery D. Molkentin: Cincinnati Children’s Hospital Medical Center

Nature Communications, 2022, vol. 13, issue 1, 1-10

Abstract: Abstract Skeletal muscle can repair and regenerate due to resident stem cells known as satellite cells. The muscular dystrophies are progressive muscle wasting diseases underscored by chronic muscle damage that is continually repaired by satellite cell-driven regeneration. Here we generate a genetic strategy to mediate satellite cell ablation in dystrophic mouse models to investigate how satellite cells impact disease trajectory. Unexpectedly, we observe that depletion of satellite cells reduces dystrophic disease features, with improved histopathology, enhanced sarcolemmal stability and augmented muscle performance. Mechanistically, we demonstrate that satellite cells initiate expression of the myogenic transcription factor MyoD, which then induces re-expression of fetal genes in the myofibers that destabilize the sarcolemma. Indeed, MyoD re-expression in wildtype adult skeletal muscle reduces membrane stability and promotes histopathology, while MyoD inhibition in a mouse model of muscular dystrophy improved membrane stability. Taken together these observations suggest that satellite cell activation and the fetal gene program is maladaptive in chronic dystrophic skeletal muscle.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-022-30619-7 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30619-7

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-30619-7

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().