DNA Methylation Analysis Reveals Distinct Patterns in Satellite Cell–Derived Myogenic Progenitor Cells of Subjects with Spastic Cerebral Palsy

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Author(s)Robinson, Karyn G.
Author(s)Marsh, Adam G.
Author(s)Lee, Stephanie K.
Author(s)Hicks, Jonathan
Author(s)Romero, Brigette
Author(s)Batish, Mona
Author(s)Crowgey, Erin L.
Author(s)Shrader, M. Wade
Author(s)Akins, Robert E.
Date Accessioned2023-02-08T13:53:12Z
Date Available2023-02-08T13:53:12Z
Publication Date2022-11-30
DescriptionThis article was originally published in Journal of Personalized Medicine. The version of record is available at: https://doi.org/10.3390/jpm12121978
AbstractSpastic type cerebral palsy (CP) is a complex neuromuscular disorder that involves altered skeletal muscle microanatomy and growth, but little is known about the mechanisms contributing to muscle pathophysiology and dysfunction. Traditional genomic approaches have provided limited insight regarding disease onset and severity, but recent epigenomic studies indicate that DNA methylation patterns can be altered in CP. Here, we examined whether a diagnosis of spastic CP is associated with intrinsic DNA methylation differences in myoblasts and myotubes derived from muscle resident stem cell populations (satellite cells; SCs). Twelve subjects were enrolled (6 CP; 6 control) with informed consent/assent. Skeletal muscle biopsies were obtained during orthopedic surgeries, and SCs were isolated and cultured to establish patient–specific myoblast cell lines capable of proliferation and differentiation in culture. DNA methylation analyses indicated significant differences at 525 individual CpG sites in proliferating SC–derived myoblasts (MB) and 1774 CpG sites in differentiating SC–derived myotubes (MT). Of these, 79 CpG sites were common in both culture types. The distribution of differentially methylated 1 Mbp chromosomal segments indicated distinct regional hypo– and hyper–methylation patterns, and significant enrichment of differentially methylated sites on chromosomes 12, 13, 14, 15, 18, and 20. Average methylation load across 2000 bp regions flanking transcriptional start sites was significantly different in 3 genes in MBs, and 10 genes in MTs. SC derived MBs isolated from study participants with spastic CP exhibited fundamental differences in DNA methylation compared to controls at multiple levels of organization that may reveal new targets for studies of mechanisms contributing to muscle dysregulation in spastic CP.
SponsorThis work was supported by the Delaware Bioscience Center for Advanced Technology; an American Academy for Cerebral Palsy and Developmental Medicine Pedal with Pete Foundation award to R.E.A.; the Delaware CTR ACCEL Program [U54–GM104941] to E.L.C.; and US National Science Foundation awards [0944557, 1316055] to A.G.M. The authors would like to thank the Nemours Foundation, Nemours Biomedical Research, and the Department of Pediatrics for institutional support of E.L.C., K.G.R., S.K.L. and R.E.A., as well as The Swank Foundation for their support to R.E.A. allowing the establishment of the neuro–orthopedic tissue repository at Nemours that provided samples for the work.
CitationRobinson, Karyn G., Adam G. Marsh, Stephanie K. Lee, Jonathan Hicks, Brigette Romero, Mona Batish, Erin L. Crowgey, M. Wade Shrader, and Robert E. Akins. “DNA Methylation Analysis Reveals Distinct Patterns in Satellite Cell–Derived Myogenic Progenitor Cells of Subjects with Spastic Cerebral Palsy.” Journal of Personalized Medicine 12, no. 12 (November 30, 2022): 1978. https://doi.org/10.3390/jpm12121978.
ISSN2075-4426
URLhttps://udspace.udel.edu/handle/19716/32238
Languageen_US
PublisherJournal of Personalized Medicine
Keywordscerebral palsy
Keywordsmuscle spasticity
Keywordsprimary cell culture
Keywordssatellite cells
Keywordsskeletal muscle
Keywordsmuscle
Keywordsskeletal
Keywordshumans
Keywordsepigenomics
KeywordsDNA methylation
Keywordsregulatory non-coding RNAs
TitleDNA Methylation Analysis Reveals Distinct Patterns in Satellite Cell–Derived Myogenic Progenitor Cells of Subjects with Spastic Cerebral Palsy
TypeArticle
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