Depletion of skeletal muscle satellite cells attenuates pathology in muscular dystrophy. Nat Commun 2022 May 26;13(1):2940
Date
05/27/2022Pubmed ID
35618700Pubmed Central ID
PMC9135721DOI
10.1038/s41467-022-30619-7Scopus ID
2-s2.0-85130718478 (requires institutional sign-in at Scopus site) 42 CitationsAbstract
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.
Author List
Boyer JG, Huo J, Han S, Havens JR, Prasad V, Lin BL, Kass DA, Song T, Sadayappan S, Khairallah RJ, Ward CW, Molkentin JDAuthor
Brian L. Lin PhD Assistant Professor in the Cell Biology Neurobiology and Anatomy department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsDisease Models, Animal
Mice
Muscle Development
Muscle, Skeletal
Muscular Dystrophies
Satellite Cells, Skeletal Muscle
Stem Cells
