Integrative genome-wide DNA methylome and transcriptome data reveals key genes involved in the dysregulation of adipose-stem cells linked to Crohn’s disease
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE217164 | GEO | 2024/09/03
REPOSITORIES: GEO
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Project description:Creeping fat, also known as mesenteric fat, which is connected to the inflamed segments of the intestine and is a hallmark of Crohn's disease (CD), appears to be correlated with disease activity. Adipose-stem cells isolated from the creeping fat of CD subjects were found to be dysfunctional (exhibiting a high inflammatory profile, high invasive and phagocytic capacities, and worse immunosuppressive properties), and this dysfunction persisted in hASCs taken from CD subjects who were in remission of the disease. We hypothesized that the abnormal behavior of adipose stem cells is caused by the accumulation of epigenetic modifications due to the inflammatory environment underlying active CD. DNA methylation and transcriptomics were performed in adipose-derived stem cells (ASCs) isolated from visceral adipose tissue biopsies of active and inactive CD patients and non-IBD patients. An integrative analysis of both omics was performed to obtain the best gene candidates.
2024-09-03 | GSE217124 | GEO
Project description:Creeping fat, also known as mesenteric fat, which is connected to the inflamed segments of the intestine and is a hallmark of Crohn's disease (CD), appears to be correlated with disease activity. Adipose-stem cells isolated from the creeping fat of CD subjects were found to be dysfunctional (exhibiting a high inflammatory profile, high invasive and phagocytic capacities, and worse immunosuppressive properties), and this dysfunction persisted in hASCs taken from CD subjects who were in remission of the disease. We hypothesized that the abnormal behavior of adipose stem cells is caused by the accumulation of epigenetic modifications due to the inflammatory environment underlying active CD. DNA methylation and transcriptomics were performed in adipose-derived stem cells (ASCs) isolated from visceral adipose tissue biopsies of active and inactive CD patients and non-IBD patients. An integrative analysis of both omics was performed to obtain the best gene candidates.
2024-09-03 | GSE217163 | GEO
Project description:Integrative genome-wide DNA methylome and transcriptome data reveals key genes involved in the dysregulation of adipose-stem cells linked to Crohn’s disease
| PRJNA897821 | ENA
Project description:Integrative genome-wide DNA methylome and transcriptome data reveals key genes involved in the dysregulation of adipose-stem cells linked to Crohn’s disease [Array]
| PRJNA896976 | ENA
Project description:Integrative genome-wide DNA methylome and transcriptome data reveals key genes involved in the dysregulation of adipose-stem cells linked to Crohn’s disease [RNA-seq]
| PRJNA897823 | ENA
Project description:Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease. However, a detailed DNA methylation (DNAme) landscape has not yet been elucidated. Our study combined DNAme and transcriptome profiles for HCM myocardium and identify aberrant DNAme associated with altered myocardial function in HCM. The transcription of methylation-related genes did not significantly differ between HCM and normal myocardium. Nevertheless, the former had an altered DNAme profile compared with the latter. The hypermethylated and hypomethylated sites in HCM tissues had chromosomal distributions and functional enrichment of correlated genes differing from those of their normal tissue counterparts. The GO analysis of network underlying the genes correlated with DNAme alteration and differentially expressed genes (DEGs) shows functional clusters centred on immune cell function and muscle system processes. In KEGG analysis, only the calcium signalling pathway was enriched either by the genes correlated with changes in DNAme or DEGs. The protein-protein interactions (PPI) underlying the genes altered at both the DNAme and transcriptional highlighted two important functional clusters. One of these was related to the immune response and had the estrogen receptor-encoding ESR1 gene as its node. The other cluster comprised cardiac electrophysiology-related genes. Intelliectin-1 (ITLN1), a component of the innate immune system, was transcriptionally downregulated in HCM and had a hypermethylated site within 1500 bp upstream of the ITLN1 transcription start site. Estimates of immune infiltration demonstrated a relative decline in immune cell population diversity in HCM. A combination of DNAme and transcriptome profiles may help identify and develop new therapeutic targets for HCM.
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Project description:Metabolites, the biochemical products of the cellular process, can be used to measure alterations in biochemical pathways related to the pathogenesis of Alzheimer's disease (AD). However, the relationships between systemic abnormalities in metabolism and the pathogenesis of AD are poorly understood. In this study, we aim to identify AD-specific metabolomic changes and their potential upstream genetic and transcriptional regulators through an integrative systems biology framework for analyzing genetic, transcriptomic, metabolomic, and proteomic data in AD. Metabolite co-expression network analysis of the blood metabolomic data in the Alzheimer's Disease Neuroimaging Initiative (ADNI) shows short-chain acylcarnitines/amino acids and medium/long-chain acylcarnitines are most associated with AD clinical outcomes, including episodic memory scores and disease severity. Integration of the gene expression data in both the blood from the ADNI and the brain from the Accelerating Medicines Partnership Alzheimer's Disease (AMP-AD) program reveals ABCA1 and CPT1A are involved in the regulation of acylcarnitines and amino acids in AD. Gene co-expression network analysis of the AMP-AD brain RNA-seq data suggests the CPT1A- and ABCA1-centered subnetworks are associated with neuronal system and immune response, respectively. Increased ABCA1 gene expression and adiponectin protein, a regulator of ABCA1, correspond to decreased short-chain acylcarnitines and amines in AD in the ADNI. In summary, our integrated analysis of large-scale multiomics data in AD systematically identifies novel metabolites and their potential regulators in AD and the findings pave a way for not only developing sensitive and specific diagnostic biomarkers for AD but also identifying novel molecular mechanisms of AD pathogenesis.
| S-EPMC9085975 | biostudies-literature
Project description: Not available
| S-SUBS9 | biostudies-other
Project description:Salmonella could survive and replicate in macrophages, where it encounters multiple stresses. Deficiency of a DNA adenine methyltransferase impairs the survival of Salmonella enterica serovar Typhimurium (S. Typhimurium) in hydrogen peroxide. To investigate whether DNA methylation is involved in the expression of oxidative stress-responsive genes, we combined RNA-seq and single-molecule real-time sequencing to integrate transcriptome and methylome analysis. Here, we show that (i) the entire amount of m6A GATC remains stable during oxidative stress; (ii) no significant association is observed between DNA methylation and transcription level in most genes; (iii) coincidence of level change between transcription and m6A GATC in the regulatory regions is identified in 49 genes under oxidative stress. Some of them are known to contribute to bacterial defenses against oxidative stress through reducing H2O2 levels, directing aberrant protein product degradation and inducing outer membrane protein expression. Specifically, the transcription level of ahpCF is negatively correlated to the m6A GATC level in its regulatory region. The transcription of smpB is elevated along with the decrease in m6A level at position 2,879,954 on the minus strand. In contrast, mRNA levels of STM14_2773 and ycfR are positively correlated with m6A GATC content in their regulatory regions. Highly stable DNA methylome and coupled change of m6A GATC with gene expression in specific positions suggest that DNA methylation homeostasis at genome-wide and plasticity in specific regions are crucial for bacterial response to oxidative stress. These findings provide new insights into the epigenetic regulatory mechanisms of gene expression in S. Typhimurium in the host microenvironment.IMPORTANCEThe intracellular pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium) comes across a wide variety of stresses from entry to dissemination, such as reactive oxygen species. To adapt itself to oxidative stress, Salmonella must adopt various and complex strategies. In this study, we revealed that DNA adenine methyltransferase was essential for S. Typhimurium to survive in hydrogen peroxide. We then screened out oxidative stress-responsive genes that were potentially regulated by DNA methylation in S. Typhimurium. Our results show that the DNA methylome is highly stable throughout the genome, and the coupled change of m6A GATC with gene expression is identified in only a few positions, which suggests the complexity of the DNA methylation and gene expression regulation networks. The results may shed light on our understanding of m6A-mediated gene expression regulation in bacteria.
| S-EPMC10715015 | biostudies-literature
Project description:BackgroundThere is considerable evidence for the importance of the DNA methylome in metabolic health, for example, a robust methylation signature has been associated with body mass index (BMI). However, visceral fat (VF) mass accumulation is a greater risk factor for metabolic disease than BMI alone. In this study, we dissect the subcutaneous adipose tissue (SAT) methylome signature relevant to metabolic health by focusing on VF as the major risk factor of metabolic disease. We integrate results with genetic, blood methylation, SAT gene expression, blood metabolomic, dietary intake and metabolic phenotype data to assess and quantify genetic and environmental drivers of the identified signals, as well as their potential functional roles.MethodsEpigenome-wide association analyses were carried out to determine visceral fat mass-associated differentially methylated positions (VF-DMPs) in SAT samples from 538 TwinsUK participants. Validation and replication were performed in 333 individuals from 3 independent cohorts. To assess functional impacts of the VF-DMPs, the association between VF and gene expression was determined at the genes annotated to the VF-DMPs and an association analysis was carried out to determine whether methylation at the VF-DMPs is associated with gene expression. Further epigenetic analyses were carried out to compare methylation levels at the VF-DMPs as the response variables and a range of different metabolic health phenotypes including android:gynoid fat ratio (AGR), lipids, blood metabolomic profiles, insulin resistance, T2D and dietary intake variables. The results from all analyses were integrated to identify signals that exhibit altered SAT function and have strong relevance to metabolic health.ResultsWe identified 1181 CpG positions in 788 genes to be differentially methylated with VF (VF-DMPs) with significant enrichment in the insulin signalling pathway. Follow-up cross-omic analysis of VF-DMPs integrating genetics, gene expression, metabolomics, diet, and metabolic traits highlighted VF-DMPs located in 9 genes with strong relevance to metabolic disease mechanisms, with replication of signals in FASN, SREBF1, TAGLN2, PC and CFAP410. PC methylation showed evidence for mediating effects of diet on VF. FASN DNA methylation exhibited putative causal effects on VF that were also strongly associated with insulin resistance and methylation levels in FASN better classified insulin resistance (AUC=0.91) than BMI or VF alone.ConclusionsOur findings help characterise the adiposity-associated methylation signature of SAT, with insights for metabolic disease risk.
| S-EPMC9290282 | biostudies-literature