ArticleCell death & disease2024
Obesity-driven mitochondrial dysfunction in human adipose tissue-derived mesenchymal stem/stromal cells involves epigenetic changes.
Article in Cell death & disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed.
- Stage-specific utility of obesity indices across the chronic kidney disease continuum.Renal failure · 2026Article
- Revitalizing Mesenchymal Stem Cells: Overcoming the Barriers of Diabetic Glucotoxicity in Regenerative Medicine.Stem cell reviews and reports · 2026Article
- Review
- 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
- The effect of weight-loss surgery in patients with obesity on adipose tissue mesenchymal stem cells versus circulating endothelial progenitor cells.International journal of obesity (2005) · 2026Article
- Pathological transcriptional retention of Cyp26b1 in perirenal adipose-derived stem cells contributes to MASLD progression.Hepatology international · 2026Article
- Mitochondrial-derived peptide MOTS-c activates metabolic signaling but blunts reparative function in human mesenchymal stromal cells.Inflammation and regeneration · 2026Article
- Identification and Transcriptomic Analysis of Mitochondria-Related Gene Signatures in Obesity.Metabolites · 2026Article
- Influence of Donor Obesity on Adipose-Derived Stem Cell Function and Therapeutic Efficacy.Cells · 2026Review
- The Impact of Large-Scale Expansion on the Functional Properties of Mesenchymal Stem Cells.Stem cell reviews and reports · 2026Review
- Maternal obesity alters adipogenic potential and mitochondrial maximal respiration in infant mesenchymal stem cells.Frontiers in endocrinology · 2026Article
- Renovascular Disease and Its Impact on Endogenous Kidney Repair: Stem/Progenitor Cells.Stem cells international · 2026Review
- Oxidoreductase delivery by cell therapies in cyclophosphamide-induced premature ovarian insufficiency: a mechanistic insight into ovarian rejuvenation.Journal of ovarian research · 2025Article
- Nutri-epigenetics of mitochondrial function and energy homeostasis in obesity.Genes & nutrition · 2025Review
- Mesenchymal Stem Cell-Mediated Targeted Drug Delivery Systems for Hepatocellular Carcinoma: Current Advances and Future Directions.Bioengineering (Basel, Switzerland) · 2025Review
- In-depth analysis of obesity-associated changes in adipose tissue-derived mesenchymal stromal/stem cells and primary cilia function.Communications biology · 2025Article
- SUV39H1 facilitate the osteogenic differentiation of dental pulp stem cells by modulating lipid metabolism and mitochondrial dynamics through FASN via non-histone methylation and ubiquitination mechanism.Stem cell research & therapy · 2025Article
- Review
- Obesity-associated macrophages dictate adipose stem cell ferroptosis and visceral fat dysfunction by propagating mitochondrial fragmentation.Nature communications · 2025Article
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Authors and funding
11 authors.
Funding
Abstract
Obesity exacerbates tissue degeneration and compromises the integrity and reparative potential of mesenchymal stem/stromal cells (MSCs), but the underlying mechanisms have not been sufficiently elucidated. Mitochondria modulate the viability, plasticity, proliferative capacity, and differentiation potential of MSCs. We hypothesized that alterations in the 5-hydroxymethylcytosine (5hmC) profile of mitochondria-related genes may mediate obesity-driven dysfunction of human adipose-derived MSCs. MSCs were harvested from abdominal subcutaneous fat of obese and age/sex-matched non-obese subjects (n = 5 each). The 5hmC profile and expression of nuclear-encoded mitochondrial genes were examined by hydroxymethylated DNA immunoprecipitation sequencing (h MeDIP-seq) and mRNA-seq, respectively. MSC mitochondrial structure (electron microscopy) and function, metabolomics, proliferation, and neurogenic differentiation were evaluated in vitro, before and after epigenetic modulation. hMeDIP-seq identified 99 peaks of hyper-hydroxymethylation and 150 peaks of hypo-hydroxymethylation in nuclear-encoded mitochondrial genes from Obese- versus Non-obese-MSCs. Integrated hMeDIP-seq/mRNA-seq analysis identified a select group of overlapping (altered levels of both 5hmC and mRNA) nuclear-encoded mitochondrial genes involved in ATP production, redox activity, cell proliferation, migration, fatty acid metabolism, and neuronal development. Furthermore, Obese-MSCs exhibited decreased mitochondrial matrix density, membrane potential, and levels of fatty acid metabolites, increased superoxide production, and impaired neuronal differentiation, which improved with epigenetic modulation. Obesity elicits epigenetic changes in mitochondria-related genes in human adipose-derived MSCs, accompanied by structural and functional changes in their mitochondria and impaired fatty acid metabolism and neurogenic differentiation capacity. These observations may assist in developing novel therapies to preserve the potential of MSCs for tissue repair and regeneration in obese individuals.
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