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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Gene expression profiles of subepithelial myofibroblasts from mouse ileum or colon, implanted together with human cancer cells in mouse xenografts

ABSTRACT: We isolated myofibroblasts from C57BL6/J mouse ileum or colon and analyzed gene expression profiles from the cultured cells. We also isolated human colon cancer cells from xenografts interacting with mouse intestinal subepithelial myofibroblasts (ISEMFs) and analyzed gene expression in sorted human cancer cells. We used Affymetrix microarrays to detail the global gene expression prolfiles in mouse fibroblasts and human colon cancer cells and identified distinct biological processes of differentially expressed genes in mouse fibroblasts and interacting human colon cancer cells For mouse SEMFs, we isolated fresh fibroblasts from mouse ileum and colon, confirmed their predicted immunophenotype (alpha SMA positive, vimentin positive, desmin negative), and expanded cells in culture before expression array analysis. We examined gene expression in human cancer cells following their interaction with murine ileal or colonic SEMFs, using flow cytometry to isolate DsRed-expressing Caco2 or T84 cells after 5 weeks of growth in NOD/SCID mice in the presence of GFP-expressing ileal or colonic SEMFs.

ORGANISM(S): Homo sapiens

SUBMITTER: Janghee Woo

PROVIDER: E-GEOD-27564 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Gene expression profiles of subepithelial myofibroblasts from mouse ileum or colon, implanted together with human cancer cells in mouse xenografts

Project description:We isolated myofibroblasts from C57BL6/J mouse ileum or colon and analyzed gene expression profiles from the cultured cells. We also isolated human colon cancer cells from xenografts interacting with mouse intestinal subepithelial myofibroblasts (ISEMFs) and analyzed gene expression in sorted human cancer cells. We used Affymetrix microarrays to detail the global gene expression prolfiles in mouse fibroblasts and human colon cancer cells and identified distinct biological processes of differentially expressed genes in mouse fibroblasts and interacting human colon cancer cells

2012-02-24 | GSE27564 | GEO

Common and distinct pathophysiological processes associated to ileal and colonic ulcers in Crohn’s disease

Project description:Based on genetic risk factors and natural history, Crohn’s disease (CD) can be separated in two entities, an ileal and a colonic disease. Protein based-approaches are needed to elucidate whether such subphenotypes are related to distinct pathophysiological processes. In this work, we compared the proteome of ulcer edge to the one of paired control tissue in ileum and colon of CD patients. We revealed that ileal and colonic ulcer edge can be distinguished by a differential distribution of epithelial–mesenchymal transition proteins, neutrophil degranulation proteins and ribosomal proteins. In ileal and colonic ulcer edge, we found a quasi-systematic increase of the proteins implicated in the pathway of protein processing in endoplasmic reticulum and a quasi-systematic decrease of mitochondrial proteins. Our study provides for the first time protein-based evidences showing partly distinct pathophysiological processes associated to ileal and colonic ulcer edge in CD. This could constitute a first step toward the development of gut segment-specific diagnostic markers and therapeutics.

2019-07-15 | PXD012284 | Pride

Structural Remodeling of the Human Colonic Mesenchyme in Inflammatory Bowel Disease [3]

Project description:Intestinal health is sustained by cooperation between diverse cell types, including epithelial cells, immune cells and stromal cells. Colonic stromal cells provide critical structural support but also regulate mucosal immunity, tolerance and inflammatory responses. Although mucosal stromal cells display substantial variability and plasticity, a paucity of unique genetic markers has precluded the identification of distinct stromal populations and functions. We used single-cell RNA-sequencing to uncover heterogeneity and subtype-specific markers of individual colonic stromal cells in health and ulcerative colitis (UC). Marker-free transcriptional clustering revealed four distinct stromal populations in healthy colon, corresponding to myofibroblasts and three previously unknown distinct subsets of fibroblasts. These fibroblast subsets were substantially remodeled in UC compared to healthy colon: inflamed UC colon was depleted for a healthy fibroblast subpopulation associated with epithelial cell homeostasis, and enriched for a novel disease-associated subtype expressing pro-inflammatory genes. Thus, we have discovered new, molecularly distinct colonic stromal cell subtypes that are altered in human disease.

2018-09-26 | GSE95450 | GEO

Structural Remodeling of the Human Colonic Mesenchyme in Inflammatory Bowel Disease [2]

2018-09-26 | GSE95446 | GEO

Structural Remodeling of the Human Colonic Mesenchyme in Inflammatory Bowel Disease [1]

2018-09-26 | GSE95435 | GEO

Gene expression profiles of subepithelial myofibroblasts from mouse ileum or colon, implanted together with human cancer cells in mouse xenografts

Project description:Gene expression profiles of subepithelial myofibroblasts from mouse ileum or colon, implanted together with human cancer cells in mouse xenografts

| PRJNA138401 | ENA

Bulk RNA-seq (>20M reads) of Intestine Epithelium (Ileum and Colon) from Satb2-deficient and WT mice

Project description:Resequening ileum and colon epithelium with deeper reads to evaluate consequence of Satb2 gene loss in the colonic epithelium. The same library construction method was used to compare with Bulk RNA-seq data from In Vitro cultured mouse organoids.

2021-10-05 | GSE167284 | GEO

Fibrosis associated changes detected in the proteome of surface epithelium overlying Crohn’s Disease Strictures

Project description:Background and aims: Intestinal fibrosis is a common complication of Crohn’s disease (CD). It is characterised by an excessive accumulation of fibroblasts differentiating into activated myofibroblasts secreting excessive extracellular matrix. The potential role of the intestinal epithelium in this fibrotic process remains poorly defined. Methods: A total of 113 CD and control subjects were studied. We performed a pilot proteomic study comparing the proteome of surface epithelium isolated by laser capture microdissection in normal and fibrotic zones of resected ileal CD strictures (n=5). Selected proteins were validated by immunohistochemistry (IHC) in colonic and ileal samples of stricturing CD patients (n=44), pure inflammatory CD (n=29) and control subjects (n=40). Functional assays with cell lines cultures and a fibroblast to myofibroblast differentiation model were used to assess the role of the highlighted epithelial proteins in CD fibrosis. Results: Proteomic study revealed an endoplasmic reticulum (ER) stress and unfolded protein response (UPR) markers increase in the epithelium overlying ileal fibrotic strictures, involving Anterior gradient protein 2 homolog (AGR2) and Binding immunoglobulin protein (BiP). This was confirmed by IHC. The ER stress induction in intestinal epithelial cells increased AGR2 as well as BiP expression and led to an extracellular secreted AGR2. A fibroblast to myofibroblast differentiation was obtained with the supernatant of intestinal epithelial cells pre-conditioned by ER stress and with recombinant AGR2. Conclusions: AGR2 and other ER stress markers are increased within the intestinal epithelium overlying fibrotic strictures and might contribute to profibrotic signals involved in CD fibrosis.

2022-04-04 | PXD022214 | Pride

Distinct Intestinal Microbial Signatures Linked to Accelerated Biological Aging in People with HIV

Project description:Genome-wide DNA methylation profiling of colon and ileal biopsies, blood samples from people living with HIV on ART and their matched HIV-negative counterparts. Despite having similar chronological ages, PWH on ART exhibit accelerated biological aging in the colon, ileum, and blood, as measured by various epigenetic aging clocks, compared to HIV-negative controls. Investigating the relationship between microbial translocation and biological aging, PWH on ART had decreased levels of tight junction proteins in the colon and ileum, along with increased microbial translocation.

2024-02-28 | GSE245924 | GEO

Crohn’s Disease Differentially Affects Region Specific Composition and Aerotolerance Profiles of Mucosally-Adherent Bacteria

Project description:BACKGROUND: The intestinal microbiota play a key role in the onset, progression, and recurrence of Crohn’s disease (CD). Most microbiome studies assay fecal material, which does not provide region-specific information on mucosally adherent bacteria that directly interact with host systems. Changes in luminal oxygen has been proposed as a contributor to CD dybiosis. METHODS: 16S rRNA data was generated using colonic and ileal mucosal from patients with CD and without inflammatory bowel diseases (nonIBD). We developed profiles reflecting bacterial abundance within defined aerotolerance categories. Bacterial diversity, composition, and aerotolerance profiles were compared across intestinal regions and disease phenotypes. RESULTS: Bacterial diversity decreased in CD in both ileum and colon. Aerotolerance profiles significantly differed between intestinal segments in nonIBD, though both were dominated by obligate anaerobes, as expected. In CD, high relative levels of obligate anaerobes were maintained in the colon and increased in the ileum. Relative abundance of similar and distinct taxa were altered in colon and ileum. Notably, several obligate anaerobes, such as Bacteroides fragilis, dramatically increased in CD in one or both intestinal segments, though specific increasing taxa varied across patients. Increased abundance of taxa from the Proteobacteria phylum was found only in the ileum. Bacterial diversity was significantly reduced in resected pre-operative tissues of patients that developed disease recurrence across two independent cohorts, with common lower abundance of bacteria from the Bacteroides, Streptococcus, and Blautia genera. CONCLUSIONS: Mucosally adherent bacteria in colon and ileum show distinct alterations in CD that provide additional insights not revealed in fecal material.

2020-04-15 | GSE147600 | GEO

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