Intestinal epithelial microvilli are abnormal in Crohn's disease
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PROVIDER: PRJNA445829 | ENA |
REPOSITORIES: ENA
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Project description:Purpose: To uncover differentially-regulated transcripts and pathways/biological processes in newly-diagnosed, pediatric Crohn's disease in comparison to healthy controls. Methods: Intestinal epithelial cells were dissociated from ileal endoscopic biopsies, and stored at -80C in RNAlater. The polyA RNA fraction was purified, and single-end, 50 bp reads were sequenced and aligned to the Hg19 genome using the TopHat2 aligner. Differential analysis was performed using Bioconductor packages including edgeR, where significance was defined as p<0.05 and fold change>2. Results: We obtained 15788 reasonably-expressed transcripts that were included in differential analyses. Conclusions: Our study characterizes the dysregulation of intestinal epithelial cells in treatment-naïve Crohn's disease using RNA sequencing for transcriptomic profile of cells obtained through ileal endoscopic biopsies.
2018-10-30 | GSE117875 | GEO
Project description:We report profiling of H3Kme3 histone modifications in intestinal epithelial cells from ileal endoscopic biopsies obtained from healthy controls and newly-diagnosed Crohn's disease (CD). We identified 1066 shared sites, corresponding to 1038 genes with increased H3K4me3 in CD, and 539 sites corresponding to 548 genes with reduced H3K4me3 in CD.
2018-10-30 | GSE117889 | GEO
Project description:Quantitative proteome profiling was performed on Inflammatory (ICD), stricturing and fistulizing Crohn's Disease serums using label-free Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS).
2017-05-15 | PXD001821 | Pride
Project description:This study investigated alterations in the transcriptomic profiles of intestinal epithelial cells in Inflammatory Bowel Diseases (IBD), i.e. Crohn's Disease and Ulcerative Colitis. Biopsies were taken from treatment-naive paediatric patients at diagnostic endoscopy from terminal ileum (TI), ascending colon (AC) and sigmoid colon (SC). Intestinal epithelial cells were purified using enzyme digestion and magnetic bead separation. RNA extraction was performed on EpCAM-positive cells, using AllPrep DNA/RNA mini kit. An Agilent Bioanalyzer was used to check RNA integrity following the manufacturer’s guidelines. mRNA was sequenced at the University of Kiel, Germany.
2017-10-16 | E-MTAB-5464 | biostudies-arrayexpress
Project description:Inflammatory Bowel Diseases are associated with marked alterations of IECs with a subsequent loss of barrier function. To identify alterations in signaling pathways in intestinal epithelium upon inflammation, we analyzed the transcriptome of IECs from patients suffering from Crohn’s disease.
2015-12-01 | GSE72780 | GEO
Project description:Biopsy samples (n=362) were collected from terminal ileum at baseline, 8 weeks after induction (Ustekinumab or placebo), and 44 weeks after maintenance (Ustekinumab 90 mg SC q12w, Ustekinumab 90 mg SC q8w, or placebo) therapies during endoscopy for RNA extraction and microarray analysis from patients with moderate-to-severe CD who participated in stelara CD phase 3 studies (UNITI-2 and IM-UNITI). These patients failed conventional therapies previously and largely naive to anti-TNF therpy. Ileum biopsies (n=26) collected from non-IBD subjects were also analyzed to serve as control. Enrichment of a core microvilli gene set was found to be reduced in UNITI-2 CD samples relative to controls, correlated with microvilli length and endoscopy score, and associated with response to treatment.
2019-03-20 | GSE112366 | GEO
Project description:Background & aimsCrohn disease (CD) presents as chronic and often progressive intestinal inflammation, but the contributing pathogenic mechanisms are unclear. We aimed to identify alterations in intestinal cells that could contribute to the chronic and progressive course of CD.MethodsWe took an unbiased system-wide approach by performing sequence analysis of RNA extracted from formalin-fixed paraffin-embedded ileal tissue sections from patients with CD (n = 36) and without CD (controls; n = 32). We selected relatively uninflamed samples, based on histology, before gene expression profiling; validation studies were performed using adjacent serial tissue sections. A separate set of samples (3 control and 4 CD samples) was analyzed by transmission electron microscopy. We developed methods to visualize an overlapping modular network of genes dysregulated in the CD samples. We validated our findings using biopsy samples (110 CD samples for gene expression analysis and 54 for histologic analysis) from the UNITI-2 phase 3 trial of ustekinumab for patients with CD and healthy individuals (26 samples used in gene expression analysis).ResultsWe identified gene clusters that were altered in nearly all CD samples. One cluster encoded genes associated with the enterocyte brush border, leading us to investigate microvilli. In ileal tissues from patients with CD, the microvilli were of decreased length and had ultrastructural defects compared with tissues from controls. Microvilli length correlated with expression of genes that regulate microvilli structure and function. Network analysis linked the microvilli cluster to several other down-regulated clusters associated with altered intracellular trafficking and cellular metabolism. Enrichment of a core microvilli gene set also was lower in the UNITI-2 trial CD samples compared with controls; expression of microvilli genes was correlated with microvilli length and endoscopy score and was associated with response to treatment.ConclusionsIn a transcriptome analysis of formalin-fixed and paraffin-embedded ileal tissues from patients with CD and controls, we associated transcriptional alterations with histologic alterations, such as differences in microvilli length. Decreased microvilli length and decreased expression of the microvilli gene set might contribute to epithelial malfunction and the chronic and progressive disease course in patients with CD.
| S-EPMC6378688 | biostudies-literature
Project description:Susceptibility to Crohn's disease, a complex inflammatory disease involving the small intestine, is controlled by over 30 loci. One Crohn's disease risk allele is in ATG16L1, a gene homologous to the essential yeast autophagy gene ATG16 (ref. 2). It is not known how ATG16L1 or autophagy contributes to intestinal biology or Crohn's disease pathogenesis. To address these questions, we generated and characterized mice that are hypomorphic for ATG16L1 protein expression, and validated conclusions on the basis of studies in these mice by analysing intestinal tissues that we collected from Crohn's disease patients carrying the Crohn's disease risk allele of ATG16L1. Here we show that ATG16L1 is a bona fide autophagy protein. Within the ileal epithelium, both ATG16L1 and a second essential autophagy protein ATG5 are selectively important for the biology of the Paneth cell, a specialized epithelial cell that functions in part by secretion of granule contents containing antimicrobial peptides and other proteins that alter the intestinal environment. ATG16L1- and ATG5-deficient Paneth cells exhibited notable abnormalities in the granule exocytosis pathway. In addition, transcriptional analysis revealed an unexpected gain of function specific to ATG16L1-deficient Paneth cells including increased expression of genes involved in peroxisome proliferator-activated receptor (PPAR) signalling and lipid metabolism, of acute phase reactants and of two adipocytokines, leptin and adiponectin, known to directly influence intestinal injury responses. Importantly, Crohn's disease patients homozygous for the ATG16L1 Crohn's disease risk allele displayed Paneth cell granule abnormalities similar to those observed in autophagy-protein-deficient mice and expressed increased levels of leptin protein. Thus, ATG16L1, and probably the process of autophagy, have a role within the intestinal epithelium of mice and Crohn's disease patients by selective effects on the cell biology and specialized regulatory properties of Paneth cells. Experiment Overall Design: 4 Samples: 2 replicates of Atg16-hypomorph Paneth cells and 2 replicates of Wildtype Paneth cells.
2008-11-15 | E-GEOD-13512 | biostudies-arrayexpress
Project description:Gene expression patterns of Crohn's disease (CD) and ulcerative colitis (UC) colonic specimens were analyzed using whole-genome microarrays. Healthy control samples were included in order to detect gene expression changes associated with CD or UC. CD and UC samples were also compared in order to identify the molecular mechanisms that distinguish both fenotypes of inflammatory bowel disease. Total RNA obtained from intestinal biopsies were analyzed using whole-genome microarrays.
2013-09-23 | E-GEOD-36807 | biostudies-arrayexpress
Project description:To investigate the gene expression profile of inflamed and non-inflamed mucosa in patients with Crohn's disease. To investigate TCR repertoires in the intestinal mucosa, the expression profile of the TCR repertoire gene was analyzed.
2022-07-19 | GSE208303 | GEO