ArticleStem cell research & therapy2023
Obesity and dyslipidemia are associated with partially reversible modifications to DNA hydroxymethylation of apoptosis- and senescence-related genes in swine adipose-derived mesenchymal stem/stromal cells.
Article in Stem cell research & therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 13 citations in OpenAlex.
- Diet and Lipidomics Mediated Regulation of Mesenchymal Stem Cell Function: Diet, Omics and Stem Cell Connection.Biomolecules · 2026Review
- Renovascular disease induces functionally relevant, locus-specific alterations to DNA methylation and hydroxymethylation in swine scattered tubular-like cells.American journal of physiology. Renal physiology · 2026Article
- Mitochondrial-derived peptide MOTS-c activates metabolic signaling but blunts reparative function in human mesenchymal stromal cells.Inflammation and regeneration · 2026Article
- Influence of Donor Obesity on Adipose-Derived Stem Cell Function and Therapeutic Efficacy.Cells · 2026Review
- Premature aging and metabolic diseases: the impact of telomere attrition.Frontiers in aging · 2025Review
- Dynamics of DNA methylation during osteogenic differentiation of porcine synovial membrane mesenchymal stem cells from two metabolically distinct breeds.Epigenetics · 2024Article
- Renovascular Disease and Mitochondrial Dysfunction in Human Mesenchymal Stem Cells.Journal of the American Society of Nephrology : JASN · 2024Article
- Senescence in Adipose-Derived Stem Cells: Biological Mechanisms and Therapeutic Challenges.International journal of molecular sciences · 2024Review
- Obesity-driven mitochondrial dysfunction in human adipose tissue-derived mesenchymal stem/stromal cells involves epigenetic changes.Cell death & disease · 2024Article
- DNA polymorphisms in inflammatory and endocrine signals linked to frailty are also associated with obesity: data from the FRASNET cohort.Frontiers in endocrinology · 2024Article
- The Impact of Obesity on Autophagy in Human Adipose-Derived Mesenchymal Stromal Cells.Cell transplantationArticle
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundObesity dysregulates key biological processes underlying the functional homeostasis, fate decisions, and reparative potential of mesenchymal stem/stromal cells (MSCs). Mechanisms directing obesity-induced phenotypic alterations in MSCs remain unclear, but emerging drivers include dynamic modification of epigenetic marks, like 5-hydroxymethylcytosine (5hmC). We hypothesized that obesity and cardiovascular risk factors induce functionally relevant, locus-specific changes in 5hmC of swine adipose-derived MSCs and evaluated their reversibility using an epigenetic modulator, vitamin-C.
methodsFemale domestic pigs were fed a 16-week Lean or Obese diet (n = 6 each). MSCs were harvested from subcutaneous adipose tissue, and 5hmC profiles were examined through hydroxymethylated DNA immunoprecipitation sequencing (hMeDIP-seq) followed by an integrative (hMeDIP and mRNA sequencing) gene set enrichment analysis. For clinical context, we compared 5hmC profiles of adipose tissue-derived human MSCs harvested from patients with obesity and healthy controls.
resultshMeDIP-seq revealed 467 hyper- (fold change ≥ 1.4; p-value ≤ 0.05) and 591 hypo- (fold change ≤ 0.7; p-value ≤ 0.05) hydroxymethylated loci in swine Obese- versus Lean-MSCs. Integrative hMeDIP-seq/mRNA-seq analysis identified overlapping dysregulated gene sets and discrete differentially hydroxymethylated loci with functions related to apoptosis, cell proliferation, and senescence. These 5hmC changes were associated with increased senescence in cultured MSCs (p16/CDKN2A immunoreactivity, senescence-associated β-galactosidase [SA-β-Gal] staining), were partly reversed in swine Obese-MSCs treated with vitamin-C, and shared common pathways with 5hmC changes in human Obese-MSCs.
conclusionsObesity and dyslipidemia are associated with dysregulated DNA hydroxymethylation of apoptosis- and senescence-related genes in swine and human MSCs, potentially affecting cell vitality and regenerative functions. Vitamin-C may mediate reprogramming of this altered epigenomic landscape, providing a potential strategy to improve the success of autologous MSC transplantation in obese patients.
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