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GSE21231
Homo sapiens
40 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Although corticosteroids remain a mainstay of therapy for UC, a meta-regression of cohort studies in acute severe ulcerative colitis (UC) showed that 29% of patients fail corticosteroid therapy and require escalation of medical management or colectomy.
Publication Title
Gene expression changes associated with resistance to intravenous corticosteroid therapy in children with severe ulcerative colitis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 46 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Cloning and variation of ground state intestinal stem cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Despite major advances with embryonic and induced pluripotent stem cells or lineage-committed, p63-expressing stem cells of stratified epithelia, we know less about the indigenous stem cells of the gastrointestinal tract, pancreas, liver, and other columnar epithelia which collectively resist cloning in their elemental states. Here we demonstrate the cloning of highly immature epithelial stem cells from defined regions of the human intestine and colon. We show that single cell-derived pedigrees can be propagated indefinitely while often sustaining minimal copy number and sequence variation. Despite prolonged cultivation, these pedigrees from disparate regions of the intestinal tract respond to identical differentiation signals by formation of epithelia with eponymous structural and gene expression features. These data suggest developmental patterning of cell-autonomous commitment programs in stem cells that enforce specialization along the gastrointestinal tract and predict the utility of these cells in disease modeling and regenerative medicine.
Publication Title
Cloning and variation of ground state intestinal stem cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Clostridium difficile (Cd) is a gram-positive, spore-forming bacterium and the primary cause of nosocomial diarrhea and pseudomembranous colitis. The pathogenicity of Cd has been linked to its production of TcdA and TcdB. While they cause fluid secretion, inflammation, and colonic damage, their respective and synergistic roles have been difficult to ascertain. In infection animal model, TcdB has been demonstrated to be a key virulence factor, and TcdB causes obvious damage in human and porcine colonic explants. Using the colonic epithelia derived from cloned colonic stem cells, we have developed a model to test the response to TcdB. Epithelia generated in air-liquid interface cultures from cloned transverse colon stem cells were challenged with TcdB at different concentrations and durations.
Publication Title
Cloning and variation of ground state intestinal stem cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Despite major advances with embryonic and induced pluripotent stem cells or lineage-committed, p63-expressing stem cells of stratified epithelia, we know less about the indigenous stem cells of the gastrointestinal tract, pancreas, liver, and other columnar epithelia which collectively resist cloning in their elemental states. Here we demonstrate the cloning of highly immature epithelial stem cells from defined regions of the human intestine and colon. In this study, we have isolated ileal stem cells and performed air-liquid interface method to induce differentiation of human ileal stem cells. The differentiated structure showed villi-like epithelia which contains enterocytes, goblet cells, endocrine cells and paneth cells.
Publication Title
Cloning and variation of ground state intestinal stem cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 143 Downloadable Samples
Description
We report ileal gene expression at diagnosis in a cohort of 210 treatment-naïve patients of pediatric Crohn''s disease and 35 non-IBD controls from the RISK study. After three years of follow-up after diagnosis, 27 of the CD patients progressed to complicated disease (B2 and/or B3). We aim to test whether Transcriptional Risk Scores helps to distinguish between patient subgroups, improving the predictive power gained from Genetic Risk Scores. Overall design: Ileal biopsies were obtained during diagnostic colonoscopies of children and adolescents (<17 years) who presented with symptoms of IBD. Non-IBD control label corresponds to those with suspected IBD, but without inflammation and normal endoscopic findings. Biopsies were stored at -80 degrees.
Publication Title
Transcriptional risk scores link GWAS to eQTLs and predict complications in Crohn's disease.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 3 Downloadable Samples
- Illumina HiSeq 2000
Description
Objective: Long non-coding RNAs (lncRNA) regulate gene transcription and diverse cellular functions. We previously defined a novel core inflammatory and metabolic ileal gene signature in treatment naïve pediatric Crohn Disease (CD), however, genome-wide characterization of lncRNA expression was lacking. We now extend our analyses to define a more comprehensive view that includes lncRNA. Design: Using RNAseq, we performed a systematic profiling of lncRNAs and protein-coding genes expression in 177 ileal biopsies. Co-expression analysis was used to identify functions and tissue-specific expression. RT-PCR was used to test lncRNAs regulation by IL-1ß in Caco-2 enterocytes model. Results: We characterize a widespread dysregulation of 459 lncRNA in the ileum of treatment naïve pediatric CD patients. Unsupervised and supervised classifications using the 459 lncRNA showed comparable patients' grouping as the 2160 dysregulated protein-coding genes, linking lncRNA to CD pathogenesis. Co-expression and functional annotation enrichment analyses across several tissues and cell types showed that the up-regulated LINC01272 is associated with a myeloid pro-inflammatory signature while the down-regulated HNF4A-AS1 exhibits association with an epithelial metabolic signature. We further validated expression and regulation of prioritized lncRNA upon IL-1ß exposure in differentiated Caco-2 cells. Finally, we identified significant correlations between LINC01272 and HNF4A-AS1 expression and more severe mucosal injury. Conclusion: We define differentially expressed lncRNA in the ileum of treatment naive pediatric CD. We show lncRNA utility to correctly classify disease or healthy states and demonstrate their regulation in response to an inflammatory signal. These lncRNA, after mechanistic exploration, may serve as potential new targets for RNA-based interventions. Overall design: Using RNAseq, we performed a systematic profiling of lncRNAs and protein-coding genes expression in 21 days differentiated caco-2 cells
Publication Title
Long ncRNA Landscape in the Ileum of Treatment-Naive Early-Onset Crohn Disease.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 172 Downloadable Samples
- Illumina HiSeq 2500
Description
RNA was isolated from rectal biopsies from 190 pediatric patients undergoing diagnostic colonoscopy for inflammatory bowel diseases, including Crohn's disease and ulcerative colitis. Single-end, 75-bp sequencing was performed, and raw reads aligned to the human genome using Gencode v 24 as reference. We included 14085 protein-coding mRNA genes in downstream analyses, where cutoffs of fold change>1.5 and FDR<0.05 were considered significant. Overall design: RNA-sequencing of rectal biopsies obtained from pediatric IBD and control patients.
Publication Title
Ulcerative colitis mucosal transcriptomes reveal mitochondriopathy and personalized mechanisms underlying disease severity and treatment response.
Sample Metadata Fields
Specimen part, Disease, Subject
View Samples