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Establishment of objective criteria for selecting relevant intestinal cell-based models

ABSTRACT: The objective of this study was to make use of gene expression signatures and functional assays to delineate differences between various intestinal colon carcinoma cell lines and normal intestinal epithelium to assess their appropriateness as a tumor model or for drug absorption studies.

ORGANISM(S): Homo sapiens

PROVIDER: GSE30292 | GEO | 2012/06/24

SECONDARY ACCESSION(S): PRJNA143599

REPOSITORIES: GEO

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Establishment of objective criteria for selecting relevant intestinal cell-based models

Project description:The objective of this study was to make use of gene expression signatures and functional assays to delineate differences between various intestinal colon carcinoma cell lines and normal intestinal epithelium to assess their appropriateness as a tumor model or for drug absorption studies. [Cell lines] Total RNA of biological replicate samples (i.e.different passages) from a panel of cell lines was collected and resulting amplified cRNA hybridized to Affymetrix Human Genome U133 Plus 2.0 arrays. Samples are labeled as follows: SampleNumber_CellLine. [Laser dissected tumor cells (LDM)] Total RNA of three different samples laser dissected tumor cells, normal colonocytes, and enterocytes of ileum and two samples of jejunum was collected and resulting amplified cRNA hybridized to Affymetrix Human Genome U133 Plus 2.0 arrays. Samples are labeled as follows: SampleNumber_TissueType_Origin.

2012-06-23 | E-GEOD-30292 | biostudies-arrayexpress

Particulate matter 10 exposure affects intestinal functionality in both inflamed 2D intestinal epithelial cell and 3D intestinal organoid models

Project description:A growing body of evidence suggests that particulate matter (PM10) enters the gastrointestinal (GI) tract directly, causing the GI epithelial cells to function less efficiently, leading to inflammation and an imbalance in the gut microbiome. PM10 may, however, act as an exacerbation factor in patients with inflamed intestinal epithelium, which is associated with inflammatory bowel disease. In this study, we established chronically inflamed intestinal epithelium models utilizing two-dimensional (2D) human intestinal epithelial cells (hIECs) and 3D human intestinal organoids (hIOs), which mimic in vivo cellular diversity and function, in order to examine the deleterious effects of PM10 in human intestine-like in vitro models. Inflamed 2D hIECs and 3D hIOs exhibited pathological features, such as inflammation, decreased intestinal markers, and defective epithelial barrier function. In addition, we found that PM10 exposure induced a more severe disturbance of peptide uptake in inflamed 2D hIECs and 3D hIOs than in control cells. This was due to the fact that it interferes with calcium signaling, protein digestion, and absorption pathways. The findings demonstrate that PM10-induced epithelial alterations contribute to the exacerbation of inflammatory disorders caused by the intestine. According to our findings, 2D hIEC and 3D hIO models could be powerful in vitro platforms for the evaluation of the causal relationship between PM exposure and abnormal human intestinal functions.

2023-07-19 | GSE227514 | GEO

The intestinal microbiota reprograms intestinal lipid metabolism through long non-coding RNA Snhg9

Project description:The intestinal microbiota is a key regulator of mammalian lipid absorption, metabolism, and storage. Here we show that the microbiota reprograms intestinal lipid metabolism in mice by repressing the expression of long non-coding RNA (lncRNA) Snhg9 in small intestinal epithelial cells. Snhg9 suppressed the activity of the transcription factor peroxisome proliferator–activated receptor γ (PPARγ) – a central regulator of lipid metabolism – by dissociating the PPARγ inhibitor Sirtuin 1 from cell cycle and apoptosis protein 2 (CCAR2). Forced expression of Snhg9 in the intestinal epithelium of conventional mice lowered dietary lipid absorption, reduced body fat, and protected against diet-induced obesity. The microbiota repressed Snhg9 expression through an immune cell signaling relay encompassing myeloid cells and innate lymphoid cells. Our findings thus identify an unanticipated role for a lncRNA in microbial control of host metabolism.

2022-07-15 | GSE208020 | GEO

Intestinal Fork Head Regulates Nutrient Absorption and Promotes Longevity

Project description:Intestinal Fork Head Regulates Nutrient Absorption and Promotes Longevity

| PRJEB22609 | ENA

HuR promotes triglyceride synthesis and intestinal fat absorption

Project description:Triacylglyceride (TAG) synthesis in the small intestine determines the absorption of dietary fat, but the mechanisms underlying are largely unknown. Here, we report that the RNA-binding protein HuR (ELAVL1) promotes TAG synthesis in the small intestine. HuR associates with the 3’UTR of Dgat2 mRNA and the introns 1 of Mgat2 pre-mRNA. Association of HuR with Dgat2 3’UTR stabilizes Dgat2 mRNA, while association of HuR with intron 1 of Mgat2 pre-mRNA promotes the processing of Mgat2 pre-mRNA. Intestinal epithelium-specific HuR knockout reduces the expression of DGAT2 and MGAT2, thereby reducing the dietary fat absorption through TAG synthesis and mitigating high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) and obesity. Our findings highlight a critical role of HuR in promoting dietary fat absorption.

2024-04-03 | GSE262777 | GEO

HuR promotes triglyceride synthesis and intestinal fat absorption

2024-01-10 | GSE252591 | GEO

RNAseq of murine small intestinal tissue following epithelium-specific deletion of Bcl9/9l +/- Apc +/- mutant B-catenin

Project description:The aim of this experiment was to determine the contribution that components of the Wnt enhancesome (Bcl9/9l) make to Wnt driven intestinal transcriptional programmes in the context of normal intestinal homeostasis, or intestinal transformation driven by Apc depletion or B-catenin mutation.

2019-01-15 | E-MTAB-7546 | biostudies-arrayexpress

Reevaluation of Criteria and Establishment of Models for Total Thyroidectomy in Differentiated Thyroid Cancer.

Project description: Not available

| S-EPMC8458835 | biostudies-literature

Intestinal lipid metabolism regulates absorption and surface of gut epithelium

Project description:Intestinal lipid metabolism regulates absorption and surface of gut epithelium

| PRJNA638157 | ENA

The transferrin receptor is required for intestinal epithelial homeostasis

Project description:The role of Tfr1 in non-erythroid tissues remains elusive due to the embryonic lethality of the Tfr1 global knockout mouse model. To bypass this problem, we generated a mouse model in which Tfr1 was conditionally deleted in intestinal epithelial cells (IECs). These mice developed severe IEC disruption, characterized by blunted villi, edema, loss of proliferative intervillus IECs, accumulation of lipids, and early neonatal lethality. Strikingly, a wide range of genes associated with epithelial-to-mesenchymal transition were highly upregulated in IEC lacking Tfr1. Additionally, candidate vesicular transport and sorting genes implicated in lipid absorption and trafficking were downregulated. Surprisingly, the presence of a mutant allele of Tfr1, which is unable to bind to iron-loaded transferrin, was capable of rescuing the lethality, intestinal epithelial homeostasis, and proliferation in a majority of the Tfr1 conditional knockout mice. 9 samples (3 wildtype, 3 knockout, 3 rescue) were prepared from the intestinal epithelial cells isolated from the small intestine and proximal colon.

2015-05-19 | E-GEOD-68984 | biostudies-arrayexpress

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