Native ECM in obesity visceral adipose tissue initiates human adipose stem cell senescence via TGF-beta and mitochondrial signaling
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE203371 | GEO | 2023/09/24
REPOSITORIES: GEO
Similar Datasets
Project description:Human adipose-derived stem/stromal cells (hASCs) can differentiate into a large broad of specialized cell types to ensure homeostasis of tissues. Thus, they are drawing increasing attention in cell therapy and regenerative medicine. However, culture conditions are still critical to ensure their regenerative capabilities. Here we compared Standard conditions (αMEM containing 10% fetal bovine serum) and Endothelial cell Growth Medium 2 (EGM2) containing few serum (2% v/v) for expansion of hASCs. Both types of hASCs were exhaustively characterized by high throughput studies, Gene Set Enrichment Analyses (GSEA) and differentiation potentials experiments. EGM2-hASCs showed enhanced multipotency and their phenotype was more immature than Standard-hASCs. The adipogenic potential of EGM2-hASCs was clearly more extented, including toward the thermogenic beige adipocyte fate. Data from microarray and GSEA highlighted Transforming Growth Factor β1 (TGFβ1) as upstream factor influencing the becoming of Standard-hASCs which is consistent with higher TGFβ1 content in Standard medium. This was associated with nuclear SMAD3 localization and higher expression of its active form in Standard-hASCs. Moreover, these cells were primed into osteoblast, chondroblast and Vascular Smooth Muscle (VSM) lineages at the expense of their adipogenic potential. Their treatment with TGFβ1 receptor inhibitors resulted in a cytoplasmic re-localization of SMAD3 and a decrease of VSM and osteoblastic lineages markers, increasing in turn their beige adipogenic potential. Therefore, TGFβ1 is a key factor committing hASCs toward osteo-chondroblastic and VSM lineages at the expanse of their beige adipogenic potential. Thanks to low TGFβ1 content, EGM2 medium improves the maintenance of uncommitted hASCs with strong beige adipocyte potential. We used microarrays to unravel differential gene expressions between human ASCs cultured in standard conditions or in EGM2 medium.
2019-09-04 | GSE136778 | GEO
Project description:Pathological expansion of adipose tissue (AT) in obesity is supported by adipocyte precursors, termed adipose-derived stromal/stem cells (ASCs). Elucidation of mechanisms underlying ASC function may lead to therapeutic interventions to treat fat mass accumulation. Using epigenome-wide association studies, we explored the impact of obesity on the methylation signature of human ASCs.
2019-12-05 | GSE111632 | GEO
Project description:Adipose stem cells (ASCs) have been widely used in preclinical and clinical trials for the treatment of various diseases. However, ASCs from people with obesity (O-ASCs) are not thoroughly investigated. In this study we aimed to evaluate the changes of the biological activity and the function of mitochondria and lysosomes in O-ASCs. We then performed gene expression profiling analysis using data obtained from RNA-seq of 2 different cells.
2023-12-06 | GSE222263 | GEO
Project description:Multipotent mesenchymal stromal cells (MSCs) have been shown to promote tissue repair and inhibit inflammatory/autoimmune responses in preclinical and human clinical trials A major problem for MSC-based therapies is the need to expand MSCs in vitro due to the low frequency of MSCs in tissues and the large numbers of cells needed/patient (1-10 x 10^6 cells/kg). The expansion of MSCs is associated with several problems including loss of homing capacity, onset of cellular senescence, decrease in differentiation capacityand susceptibility to genomic instability and malignant transformation, limiting the utility of MSCs as a cell-based therapy. We have recently reported that murine adipose tissue-derived MSCs (mASCs) and human ASCs (hASCs) express glycoprotein A repetitions predominant (GARP)/leucine-rich repeat-containing 32 (LRRC32). GARP binds LAP/TGF-β1 to the surface of mASCs and hASCs, regulating their secretion and activation of TGF-β1 and promoting their immunomodulatory capacity. Interestingly, silencing of GARP in ASCs significantly decreased their proliferative capacity but the mechanisms remain unknown. As the proliferative capacity of MSCs is fundamental for their success in therapy, we have aimed at understanding how GARP modulates the expansion of MSC.
2019-06-05 | GSE104254 | GEO
Project description:The role of obesity in endometrial cancer development is tested by co-culturing adipose stromal cells (ASCs) with endometrial epithelial cells and endometrial cancer cell Ishikawa for 21 days. Control cells (not exposed to ASCs) were incubated for the same duration. RNA-seq identified differential expression due to ASC exposure
2019-02-13 | GSE103203 | GEO
Project description:identification of the effect of transgenerationnal supplementation with omega 3 fatty acids on the resistance to a diet induced obesity challenge identification of the effect of transgenerationnal supplementation with omega 3 fatty acids on the resistance to a diet induced obesity challenge
2021-12-01 | GSE176356 | GEO
Project description:The epigenome of stem cells occupies a critical interface between genes and environment, serving to regulate expression through modification by intrinsic and extrinsic factors. We hypothesized that aging and obesity, which represent major risk factors for a variety of diseases, synergistically modify the epigenome of adult adipose stem cells (ASCs). Using integrated RNA- and targeted bisulfite-sequencing in murine ASCs from lean and obese mice at 5- and 12-months of age, we identified global DNA hypomethylation with either aging or obesity, and a synergistic effect of aging combined with obesity. The transcriptome of ASCs in lean mice was relatively stable to the effects of age, but this was not true in obese mice. Functional pathway analyses identified a subset of genes with critical roles in progenitors and in diseases of obesity and aging. Specifically, Mapt, Nr3c2, App, and Ctnnb1 emerged as potential hypomethylated upstream regulators in both aging and obesity (AL vs. YL and AO vs. YO), and App, Ctnnb1, Hipk2, Id2, and Tp53 exhibited additional effects of aging in obese animals. Furthermore, Foxo3 and Ccnd1 were potential hypermethylated upstream regulators of healthy aging (AL vs. YL), and of the effects of obesity in young animals (YO vs. YL), suggesting that these factors could play a role in accelerated aging with obesity. Finally, we identified candidate driver genes that appeared recurrently in all analyses and comparisons undertaken. Further mechanistic studies are needed to validate the roles of these genes capable of priming ASCs for dysfunction in aging- and obesity-associated pathologies.
2023-12-21 | GSE251721 | GEO
Project description:The epigenome of stem cells occupies a critical interface between genes and environment, serving to regulate expression through modification by intrinsic and extrinsic factors. We hypothesized that aging and obesity, which represent major risk factors for a variety of diseases, synergistically modify the epigenome of adult adipose stem cells (ASCs). Using integrated RNA- and targeted bisulfite-sequencing in murine ASCs from lean and obese mice at 5- and 12-months of age, we identified global DNA hypomethylation with either aging or obesity, and a synergistic effect of aging combined with obesity. The transcriptome of ASCs in lean mice was relatively stable to the effects of age, but this was not true in obese mice. Functional pathway analyses identified a subset of genes with critical roles in progenitors and in diseases of obesity and aging. Specifically, Mapt, Nr3c2, App, and Ctnnb1 emerged as potential hypomethylated upstream regulators in both aging and obesity (AL vs. YL and AO vs. YO), and App, Ctnnb1, Hipk2, Id2, and Tp53 exhibited additional effects of aging in obese animals. Furthermore, Foxo3 and Ccnd1 were potential hypermethylated upstream regulators of healthy aging (AL vs. YL), and of the effects of obesity in young animals (YO vs. YL), suggesting that these factors could play a role in accelerated aging with obesity. Finally, we identified candidate driver genes that appeared recurrently in all analyses and comparisons undertaken. Further mechanistic studies are needed to validate the roles of these genes capable of priming ASCs for dysfunction in aging- and obesity-associated pathologies.
2023-12-21 | GSE251720 | GEO
Project description:Background & Aims: Obesity is the most important risk factor and a potential treatment target for fatty liver disease (FLD). The continuous adaptation or ‘remodelling’ of hepatic mitochondrial flexibility plays a key role in the pathogenesis of FLD. Human adipose stem cell (hASC)-derived hepatocyte-like cells (HLCs) offer attractive tools for the research and therapy of liver dysfunction. However, evidence showing the ‘remodelling’ of hepatic mitochondrial flexibility or differentiation capability of hASCs in obese patients is lacking. Methods: The differentiation capability and mitochondrial structure and function of hepatic cells were evaluated by measuring gene expression, de novo lipogenesis and mitochondrial respiration in HLCs derived from hASCs of obese patients and lean controls. The ability of the GSK3 inhibitor CHIR-99021 to modify the mitochondrial oxidative dysfunction was evaluated in the HLCs derived from the hASCs of obese patients. Results: hASCs from obese patients showed the potential to differentiate into HLCs. HLCs from the hASCs of obese patients exhibited the characteristics of hepatic steatosis, lower expression of the subunits of mitochondrial complex I and lower oxidative phosphorylation levels. CHIR-99021 promoted the expression of NDUFB8, NDUFB9, the subunits of mitochondrial complex I, and the basal oxygen consumption rate of the HLCs derived from the hASCs of obese patients by upregulating the expression of PGC-1α, the transcription factor involved in mitochondrial biogenesis and ‘remodelling’. Conclusions: The results demonstrate that obese patient ASC-derived HLCs had mitochondrial oxidative dysfunction, which may represent the consequence of hepatic steatosis.
2021-03-19 | GSE151760 | GEO
Project description:Visceral white adipose tissue (VAT) is susceptible to inflammation as a result of obesity, and this inflammation contributes to the development of obesity-related diseases. During the development of obesity, inflammatory immunocytes, including CD8+ T cells, Th1 cells, M1-like macrophages, neutrophils, and mast cells, accumulate in VAT. While these profound changes in the immunocyte composition of VAT lead to local inflammation, the triggers of VAT inflammation remain poorly understood. Therefore, a better understanding of the mechanisms underlying an early event of obesity-associated VAT inflammation will contribute to the development of novel therapies for obesity-related diseases. We utilized CellChat, which employs the expression of ligand-receptor pairs as indicators of intercellular communications, to examine the potential impact of these identified cell types within SVF on T cells. Our analysis revealed that ASCs exert the greatest influence on T cells in both lean and obese conditions. Finally, we demonstrated that ASCs promote Tcell infiltration into WAT during the early stages of obesity.
2023-10-01 | GSE237143 | GEO