ArticleBMC medicine2017
Abnormal epigenetic changes during differentiation of human skeletal muscle stem cells from obese subjects.
Article in BMC medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 76 citations in OpenAlex.
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- New insights into the role of metallothioneins in obesity and diabetes.International journal of obesity (2005) · 2025Review
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- DNA methylation of exercise-responsive genes differs between trained and untrained men.BMC biology · 2024Article
- Metabolic memory: mechanisms and diseases.Signal transduction and targeted therapy · 2024Review
- The influence of host genotype and gut microbial interactions on feed efficiency traits in pigs.Frontiers in microbiology · 2024Article
- Research progress on the effects of adverse exposure during pregnancy on skeletal muscle function in the offspring.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2023Review
- DNA methylation profiling reveals novel pathway implicated in cardiovascular diseases of diabetes.Frontiers in endocrinology · 2023Article
- Immune modulation and prognostic significance of MCM10 in pan-cancer: a comprehensive analysis.American journal of translational research · 2023Article
- TLR4 activation inhibits the proliferation and osteogenic differentiation of skeletal muscle stem cells by downregulating LGI1.Journal of physiology and biochemistry · 2022Article
- A pilot investigation of genetic and epigenetic variation of FKBP5 and response to exercise intervention in African women with obesity.Scientific reports · 2022Article
- Epigenetics of type 2 diabetes mellitus and weight change - a tool for precision medicine?Nature reviews. Endocrinology · 2022Review
- Maternal undernutrition alters the skeletal muscle development and methylation of myogenic factors in goat offspring.Animal bioscience · 2022Article
- Skeletal muscle-targeted delivery of Fgf6 protects mice from diet-induced obesity and insulin resistance.JCI insight · 2021Article
- Article
- VPS39-deficiency observed in type 2 diabetes impairs muscle stem cell differentiation via altered autophagy and epigenetics.Nature communications · 2021Article
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- Epigenetic modifications in muscle regeneration and progression of Duchenne muscular dystrophy.Clinical epigenetics · 2021Review
- Global DNA methylation pattern involved in the modulation of differentiation potential of adipogenic and myogenic precursors in skeletal muscle of pigs.Stem cell research & therapy · 2020Article
Corrections and comments
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Authors and funding
20 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHuman skeletal muscle stem cells are important for muscle regeneration. However, the combined genome-wide DNA methylation and expression changes taking place during adult myogenesis have not been described in detail and novel myogenic factors may be discovered. Additionally, obesity is associated with low relative muscle mass and diminished metabolism. Epigenetic alterations taking place during myogenesis might contribute to these defects.
methodsWe used Infinium HumanMethylation450 BeadChip Kit (Illumina) and HumanHT-12 Expression BeadChip (Illumina) to analyze genome-wide DNA methylation and transcription before versus after differentiation of primary human myoblasts from 14 non-obese and 14 obese individuals. Functional follow-up experiments were performed using siRNA mediated gene silencing in primary human myoblasts and a transgenic mouse model.
resultsWe observed genome-wide changes in DNA methylation and expression patterns during differentiation of primary human muscle stem cells (myoblasts). We identified epigenetic and transcriptional changes of myogenic transcription factors (MYOD1, MYOG, MYF5, MYF6, PAX7, MEF2A, MEF2C, and MEF2D), cell cycle regulators, metabolic enzymes and genes previously not linked to myogenesis, including IL32, metallothioneins, and pregnancy-specific beta-1-glycoproteins. Functional studies demonstrated IL-32 as a novel target that regulates human myogenesis, insulin sensitivity and ATP levels in muscle cells. Furthermore, IL32 transgenic mice had reduced insulin response and muscle weight. Remarkably, approximately 3.7 times more methylation changes (147,161 versus 39,572) were observed during differentiation of myoblasts from obese versus non-obese subjects. In accordance, DNMT1 expression increased during myogenesis only in obese subjects. Interestingly, numerous genes implicated in metabolic diseases and epigenetic regulation showed differential methylation and expression during differentiation only in obese subjects.
conclusionsOur study identifies IL-32 as a novel myogenic regulator, provides a comprehensive map of the dynamic epigenome during differentiation of human muscle stem cells and reveals abnormal epigenetic changes in obesity.
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