Browse
Submit Data
Databases
API
Help

Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

136 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Altered MHC class 1 DNA methylation of intestinal epithelial stem cells contributes to chronic inflammation in Crohn’s Disease

ABSTRACT: Altered function of the intestinal epithelium has been considered to play a key role in CD pathogenesis, however exact mechanisms that contribute towards lifelong relapsing mucosal inflammation remain ill defined. DNA methylation (DNAm) is a key epigenetic mechanism known to determine cellular identity by regulating gene transcription with alterations increasingly being implicated in IBD pathogenesis. We generated 312 intestinal epithelial organoids (IEOs) from mucosal stem cells obtained from 168 patients diagnosed with CD, non-IBD/healthy controls and Ulcerative colitis (UC). Genome wide epigenetic profiling of IEOs and primary purified epithelium revealed highly stable, CD associated loss of DNAm in MHC-I related genes which correlated with increased gene expression. Related Single Cell Portal accession number: SCP1884 Related Gene Expression Omnibus accession numbers: GSE57945, GSE75214

ORGANISM(S): Homo sapiens

SUBMITTER: Felicity Payne

PROVIDER: E-MTAB-12841 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

Ascending colon biopsies from pediatric patients

Project description:We sought to identify proteins that enable differentiation between CD and UC in children with new onset IBD. Mucosal biopsies were obtained from children undergoing baseline diagnostic endoscopy prior to therapeutic interventions. Using a super-stable isotope labeling with amino acids in cell culture (SILAC)-based approach, the proteomes of 99 paediatric control and biopsies of patients with CD and UC were compared. Multivariate analysis of a subset of these (n=50) was applied to identify novel biomarkers, which were validated in a second subset (n=49). In the discovery cohort, a panel of five proteins was sufficient to distinguish control from IBD-affected tissue biopsies with an AUC of 1.0 (95% CI 0.99 to 1.0); a second panel of 12 proteins segregated inflamed CD from UC within an AUC of 0.95 (95% CI 0.86 to 1.0). Application of the two panels to the validation cohort resulted in accurate classification of 95.9% (IBD from control) and 80% (CD from UC) of patients. 116 proteins were identified to have correlation with the severity of disease, four of which were components of the two panels, including visfatin and metallothionein-2. This study has identified two panels of candidate biomarkers for the diagnosis of IBD and the differentiation of IBD subtypes to guide appropriate therapeutic interventions in paediatric patients.

2018-11-06 | PXD005086 | Pride

DNA methylation profiling of intestinal epithelial cells from paediatric biopsies including Inflammatory Bowel disease and healthy controls

Project description:We purified the intestinal epithelial cells from biopsies taken from the ileum and colon of a paediatric cohort of IBD patients and healthy controls

2017-10-20 | E-MTAB-5463 | biostudies-arrayexpress

RNA-sequencing of coding RNA from human purified intestinal epithelial samples and organoids derived from foetal and paediatric small and large intestine

Project description:Human intestinal epithelial organoids (IEO) culture models are rapidly emerging as novel experimental tools to investigate fundamental aspects of intestinal epithelial (patho)physiology. Cellular source and culture protocols vary between different IEO models and reliable markers for their characterization/validation are currently limited. Here, we provide the following reference datasets of transcriptomic profiling by RNA-sequencing: Purified intestinal epithelial cells (EpCAM+) from paediatric ileum and colon, Intestinal organoid cultures from paediatric ileum and colon, Purified intestinal epithelial cells (EpCAM+) from foetal small intestine and foetal large intestine, Intestinal organoid cultures from foetal small intestine and foetal large intestine, Intestinal organoid cultures derived from induced pluripotent stem cells.<br> Complementary data from methylation profiling on the same samples have been deposited at ArrayExpress under accession number E-MTAB-4957 ( https://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-4957 ).</br>

2018-01-20 | E-MTAB-5015 | biostudies-arrayexpress

Predicting response to vedolizumab therapy using mucosal transcriptomics in IBD patients

Project description:In this study we wanted to identify baseline predictors of successful vedolizumab therapy in patients with inflammatory bowel disease.

2019-08-23 | E-MTAB-7845 | biostudies-arrayexpress

A functional genomics predictive network model identifies regulators of inflammatory bowel disease: Microarray Analysis of Human Blood and Intestinal Biopsy Samples from a Phase 2b, Double-blind, Placebo-controlled Study of Ustekinumab in Crohn's Disease

Project description:Microarray Analysis of Human Whole Blood and Intestinal Biopsy Samples from a Phase 2b, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study of Ustekinumab in Crohn’s Disease 329 Crohn's biopsies from multiple regions in the intestine of 87 anti TNFa refractory patients and blood samples from 204 patients at Week 0 prior to drug treatment are included in this study

2017-07-07 | E-GEOD-100833 | biostudies-arrayexpress

Quantitative LC-MS/MS Proteomics of human small intestine

Project description:The objective was to determine the expression of a wide range proteins pertinent to metabolism and disposition of chemicals and nutrients in the intestinal epithelium. Ileum and jejunum biopsy specimens were obtained from 16 patients undergoing gastrointestinal elective surgery. Mucosal fractions were prepared and analysed using targeted and global proteomic approaches. A total of 29 enzymes, 32 transporters, 6 tight junction proteins, 2 adhesion proteins, alkaline phosphatase, thioredoxin, 5 markers and 1 regulatory protein were quantified; 60 for the first time.

2021-09-09 | PXD020987 | Pride

A proteome analysis by LC-MS/MS of human colon mucosal biopsies from gastrointestinal healthy rheumatoid arthritis patients

Project description:The joint disease rheumatoid arthritis (RA) is characterized by persistent synovitis, leading to cartilage damage, bone erosion, and ultimately impaired joint function. The disease affects 0.5 to 1.0% of adults in developed countries, and is three times more frequent in women than in men. A number of autoantibodies can be detected in RA patient’s serum targeting the patient’s own proteins. Several of these proteins, including rheumatoid factor, can also be detected in patients suffering from other autoimmune diseases, including the inflammatory bowel diseases (IBD). IBD and RA share several genetic risk logi, an altered gut microbiota, and environmental risk factors. Articular involvement is the most common extra-intestinal manifestation in patients diagnosed with IBD, with a prevalence between 17 to 39%. Additionally, methotrexate (MTX) is the most frequently prescribed immunosuppressive drug for RA and the second most for the IBD, indicating close similarities between the two diseases. We, therefore, characterized the protein content (the proteome) of the colon mucosa of gastrointestinal healthy RA patients, to investigate if we could detect IBD-related changes. The LC-MS/MS analysis was conducted as part of a previous study (ProteomeXChange submission PXD001608), enabling a comparison between the two datasets, containing the colon mucosal proteome of 11 RA patients, 10 IBD (ulcerative colitis) patients, and 10 controls. This data submission covers the triplicate proteome analysis of the colon mucosa of 11 gastrointestinal healthy RA patients.

2016-09-26 | PXD003082 | Pride

RNA-seq of nonstenotic and stenotic areas of patients with Crohn’s disease

Project description:Fibrostenotic disease is a common complication in Crohn’s disease (CD). We performed bulk RNA sequencing (n=16) of paired intestinal biopsies taken from nonstenotic and stenotic areas of patients with CD (n=8).

2023-04-26 | E-MTAB-12788 | biostudies-arrayexpress

Single-cell sequencing of developing human gut reveals transcriptional links to childhood Crohn’s disease

Project description:In this study, we performed single-cell transcriptional profiling of human embryonic and fetal gut samples obtained from 9 human embryos spanning ages 6-10 PCW and three regions (duo-jejunum, ileum and colon). Additionally, we profile mucosal biopsies from the terminal ileum of healthy children aged 4-12 years (n = 8) as well as a group of children newly diagnosed with Crohn’s disease (CD) (n = 7), a common form of IBD. Tissue samples were treated using an enzymatic dissociation protocol and single cell suspensions were then processed using the 3’v2 10x Genomics Chromium workflow. In a subset of samples, the intestinal epithelial cell fraction was enriched by performing magnetic bead sorting for EPCAM. In total, we generate single cell transcriptomes of ~90,000 primary human intestinal cells providing a rich resource and detailed roadmap. Using this data as well as scRNAseq profiles of human fetal gut derived organoids we describe embryonic and fetal epithelium composition, trace their differentiation dynamics and signaling partners, and provide links to regenerating Crohn’s disease epithelium.

2020-12-22 | E-MTAB-8901 | biostudies-arrayexpress

RNA-seq of biopsies, crypts and organoids of inflamed and non-inflamed biopsies of ulcerative colitis patients

Project description:Patient-derived intestinal organoids provide an excellent tool to unravel mechanisms underlying ulcerative colitis (UC). Fresh biopsies, to isolate crypts and culture organoids, were obtained from both inflamed and non-inflamed regions from eight patients with active UC (Mayo endoscopic subscore ≥2), and from eight non-IBD controls.To address the inflammatory character of ex vivo organoids, we compared the transcriptome of biopsies, crypts and organoids derived from inflamed, and non-inflamed regions and aimed to (re-)induce inflammation ex vivo.

2020-10-08 | E-MTAB-7860 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data