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Aging and obesity prime the methylome and transcriptome of adipose stem cells for disease and dysfunction [RNA-seq]

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE251721 | GEO | 2023/12/21

REPOSITORIES: GEO

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Aging and obesity prime the methylome and transcriptome of adipose stem cells for disease and dysfunction [Methyl-seq]

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

Genome-wide analysis reveals DNA methylation markers that varies with both age and obesity

Project description:Background: The obesity epidemic and the aging population of many western countries together with their associated diseases are major challenges for the healthcare. As obesity is a risk factor for many age related diseases, such as cancer, it is of importance to understand their interaction and the underlying molecular mechanisms. Lately, epigenetic programming in the form of DNA methylation and have been recognized for its importance in aging, obesity and several diseases. Method: Herein, the methylation level was determined for around 27000 CpG-islands in 46 DNA samples from adult peripheral blood with microarrays. The dependence for each CpG island with age, obesity and their interaction was ascertained with a general linear model. Results: The methylation level of more than 100 genomic sites were significantly altered with increasing age together with 10 additional sites that were differentially methylated with age in obese and lean individuals. The majority of the genomic sites were hypermethylated during aging, including the telomerase catalytic subunit (TERT). However, age dependent hypermethylation was prohibited or reverted in 8 of 10 regions in obese where an interaction between age and obesity was observed. Moreover, one region (LINC00304) was differentially methylated in obese and lean. Conclusion: This study provides evidence for an obesity influence on age driven epigenetic changes, which provide a molecular link between aging and obesity. This link and the identified markers may prove to be valuable biomarkers for the understanding of the molecular basis of aging, obesity and associated diseases. Bisulphite converted DNA from the 24 obese and 22 lean women were hybridised to the Illumina Infinium 27k Human Methylation Beadchip v1.2

2014-07-09 | E-GEOD-44763 | biostudies-arrayexpress

Native ECM in obesity visceral adipose tissue initiates human adipose stem cell senescence via TGF-beta and mitochondrial signaling

Project description:Background & Aims: Obesity is a complex disease that causes visceral WAT dysfunction and is associated with cardiovascular, chronic inflammatory and other metabolic pathologies.Adipose-derived stem cells (ASCs) are the key cells for adipose tissue homeostasis.However, how obesity may affect the biological functions of hASCs is not clear. We then performed gene expression profiling analysis using data obtained from RNA-seq of 8 different donors obese group,and 3 different donors lean group

2023-09-24 | GSE203371 | GEO

Expression profiling in adipocytes of obese humans

Project description:Microarray analysis comparing gene expression profiles of adipocytes from non-diabetic lean vs non-diabetic obese Pima Indian subjects to identify differentially expressed adipocyte genes with obesity. RNA samples of isolated abdominal subcutaneous adipocytes from 20 lean (10 Males / 10 Females, aged 31±6 year, Body Mass Index 25±3 kg/m2 ) and 19 obese (9M/10F, 29±5y, 55±8 kg/m2 ) subjects were hybridized individually to Affymetrix oligonucleotide arrays HG-U95A, B, C, D, and E. Keywords = adipocyte Keywords = obesity Keywords = inflammation Keywords = gene expression Keywords: other

2006-01-01 | GSE2508 | GEO

Transcription profiling of human abdominal subcutaneous adipocytes from obese and non-obese Pima Indians

Project description:Microarray analysis comparing gene expression profiles of adipocytes from non-diabetic lean vs non-diabetic obese Pima Indian subjects to identify differentially expressed adipocyte genes with obesity. RNA samples of isolated abdominal subcutaneous adipocytes from 20 lean (10 Males / 10 Females, aged 31Â±6 year, Body Mass Index 25Â±3 kg/m2 ) and 19 obese (9M/10F, 29Â±5y, 55Â±8 kg/m2 ) subjects were hybridized individually to Affymetrix oligonucleotide arrays HG-U95A, B, C, D, and E.

2007-08-25 | E-GEOD-2508 | biostudies-arrayexpress

Genome-wide analysis reveals DNA methylation markers that varies with both age and obesity

2014-07-09 | GSE44763 | GEO

Single-cell transcriptome of stromal vascular fraction isolated from adipose tissue of lean and obese mice

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

Expression profiling in preadipocytes in obese Pima Indians/humans

Project description:Microarray analysis comparing gene expression profiles of primary cultured preadipocytes from non-diabetic lean vs non-diabetic obese Pima Indian subjects (a subset of the subjects from the adipocyte genechip project, GSE2508). Primary cultured abdominal subcutaneous preadipocytes from 14 lean (7 Males / 7 Females) and 14 obese (7M/7F) subjects were hybridized individually to Affymetrix oligonucleotide arrays HG-U133A and B. Keywords = Obesity Keywords = inflammation Keywords = microarray Keywords = gene expression Keywords = preadipocyte Keywords = stromal-vascular cells Keywords = adipose tissue Keywords: other

2005-07-28 | GSE2510 | GEO

Gene expression microarray profiles of cumulus cells in lean and overweight-obese polycystic ovary syndrome patients

Project description:Objective: The etiology of PCOS is mostly unknown. Existing data support both genetic and environmental factors in its pathogenesis. Design: Prospective case - control study. Setting: University Hospital. Patients: 25 patients undergoing IVF-ICSI treatment. Intervention: Genome-wide oligonucleotide microarray technology was used to study differential gene-expression patterns of cultured human cumulus cells from IVF patients divided into 4 groups according to disease state (PCOS vs. Control) and BMI (Obese vs. Lean). Results: Two differential PCOS gene expression profiles were established: Lean-Type was formed by comparing PCOS lean (PL) vs. non-PCOS lean (NL) individuals; Obese-Type was formed by comparing PCOS obese (PO) vs. non-PCOS (NO) obese patients. Conclusions: Different molecular pathways are associated with PCOS in Lean and Obese individuals, as demonstrated by gene expression profiling of cumulus cells. Our findings provide insights into the molecular pathogenesis of PCOS. We used microarrays to study the gene expression of human cultured cumulus cells. We compared the genes expression of lean PCOS, Obese PCOS, lean controls and obese controls. Different molecular pathways are associated with PCOS in Lean and Obese patients. Keywords: disease state analysis

2008-03-27 | GSE10946 | GEO

Human AsPC1-CFP and AsPC1-AKT PDAC orthotopic tumors: Lean vs Obese

Project description:Transcriptional profiling comparing human AsPC1 PDA cells transduced with either CFP control or myristoylated-AKT orthotopically grown in pancreata of lean vs obese Rag1-/- immunodeficient mice for 5 weeks (100,000 cells/pancreas). The Goal was to determine the transcriptional deregulation of Obesity-driven and AKT-driven tumors.

2017-05-26 | GSE99289 | GEO

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