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GSE49877
Homo sapiens
36 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The intestinal mucosa harbors the largest accumulation of T lymphocytes in the body. While these T cells play an important role in immune homeostasis, they are also implicated in triggering and maintaining pathological intestinal inflammation. In humans they are poorly characterised, and even mouse transcriptomes have been reported for only a few individual cell types, many of which lack direct human equivalents. Using expression microarrays on T cells isolated from ileal biopsies and in silico analysis, we present here an unbiased, transcriptome-wide view of function in T cell subpopulations of the healthy human intestine and delineate signalling pathways that are distinct from those seen in peripheral blood T cells.
Publication Title
Generation of primary human intestinal T cell transcriptomes reveals differential expression at genetic risk loci for immune-mediated disease.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
XBP1 is the transcriptino factor that is activated by the ER stress. XBP1 is known to induce the ER dexpansion and increase the expression of the ER chaperone genes to prtect the cell from the ER stress. We generated a mouse strain that lacked XBP1 specifically in the mouse intestine by breeding the XBP1flox mice with Villin-cre mice. Here we examined genes that are differentially expressed between WT and XBP1 KO mouse intestine to identify genes that are downstream of XBP1.
Publication Title
XBP1 links ER stress to intestinal inflammation and confers genetic risk for human inflammatory bowel disease.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The role of peroxisome proliferator-activated receptor (PPAR) activation on global gene expression and mitochondrial fuel utilization were investigated in human myotubes. Only 21 genes were up-regulated and 3 genes were down-regulated after activation by the PPAR agonist GW501516. Pathway analysis showed up-regulated mitochondrial fatty acid oxidation, TCA cycle and cholesterol biosynthesis. GW501516 increased oleic acid oxidation and mitochondrial oxidative capacity by 2-fold. Glucose uptake and oxidation were reduced, but total substrate oxidation was not affected, indicating a fuel switch from glucose to fatty acid. Cholesterol biosynthesis was increased, but lipid biosynthesis and mitochondrial content were not affected. This study confirmed that the principal effect of PPAR activation was to increase mitochondrial fatty acid oxidative capacity. Our results further suggest that PPAR activation reduced glucose utilization through a switch in mitochondrial substrate preference by up-regulating pyruvate dehydrogenase kinase isozyme 4 and genes involved in lipid metabolism and fatty acid oxidation.
Publication Title
PPARδ activation in human myotubes increases mitochondrial fatty acid oxidative capacity and reduces glucose utilization by a switch in substrate preference.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Here we describe a method for fabricating a primary human Small Intestine-on-a-Chip (Intestine Chip) containing epithelial cells isolated from healthy regions of intestinal biopsies. The primary epithelial cells are expanded as 3D organoids, dissociated, and cultured on a porous membrane within a microfluidic device with human intestinal microvascular endothelium cultured in a parallel microchannel under flow and cyclic deformation. In the Intestine Chip, the epithelium forms villi-like projections lined by polarized epithelial cells that undergo multi-lineage differentiation similar to that of intestinal organoids, however, these cells expose their apical surfaces to an open lumen and interface with endothelium. Transcriptomic analysis also indicates that the Intestine Chip more closely mimics whole human duodenum in vivo when compared to the duodenal organoids used to create the chips. Because fluids flowing through the lumen of the Intestine Chip can be collected continuously, sequential analysis of fluid samples can be used to quantify nutrient digestion, mucus secretion and establishment of intestinal barrier function over a period of multiple days in vitro. The Intestine Chip therefore may be useful as a research tool for applications where normal intestinal function is crucial, including studies of metabolism, nutrition, infection, and drug pharmacokinetics, as well as personalized medicine.
Publication Title
Development of a primary human Small Intestine-on-a-Chip using biopsy-derived organoids.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
Illumina HiSeq 3000
Description
A coding variant of the inflammatory bowel disease (IBD) risk gene ATG16L1 has been associated with defective autophagy and deregulation of endoplasmic reticulum (ER) function. IL-22 is a barrier protective cytokine by inducing regeneration and antimicrobial responses in the intestinal mucosa. We show that ATG16L1 critically orchestrates IL-22 signaling in the intestinal epithelium. IL-22 stimulation physiologically leads to transient ER stress and subsequent activation of STING dependent type I interferon (IFN-I) signaling, which is augmented in Atg16l1?IEC intestinal organoids. IFN-I signals amplify epithelial TNF production downstream of IL-22 and contribute to necroptotic cell death. In vivo, IL-22 treatment in Atg16l1?IEC and Atg16l1?IEC/Xbp1?IEC mice potentiates endogenous ileal inflammation and causes widespread necroptotic epithelial cell death. Therapeutic blockade of IFN-I signaling ameliorates IL-22 induced ileal inflammation in Atg16l1?IEC mice. Our data demonstrate an unexpected role of ATG16L1 in coordinating the outcome of IL-22 signaling in the intestinal epithelium. Overall design: Organoids from Atg16l intestinal knockout vs. Wildtype
Publication Title
ATG16L1 orchestrates interleukin-22 signaling in the intestinal epithelium via cGAS-STING.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Treatment induced senescence (TIS) is a terminal cell cycle arrest program, increasingly recognized as a tumor suppressor mechanism complementing apoptosis in response to standard chemotherapy regimens. In particular cells with blocked apoptotic pathways rely on senescence as the only remaining failsafe mechanism to keep the neoplastic growth in check. However, little is known about biological properties, long-term fate of senescent tumor cells and their impact on the microenvironment.
Publication Title
Opposing roles of NF-κB in anti-cancer treatment outcome unveiled by cross-species investigations.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 100 Downloadable Samples
- Illumina human-6 v2.0 expression beadchip
Description
Gene expression data from 100 human hepatocellular carcinomas (HCC) were generated and analyzed as part of effort for validating prognostic gene expression signatures from previous studies. Using four different classification algorithms and leave-one-out cross-validation approaches, four different prognostic signatures were applied to test the robustness and concordance of predicted outcome in individual patients. All four tumor-derived signatures were significantly associated with prognosis and had a high rate of concordance with predicted outcomes for individual patients.
Publication Title
Sixty-five gene-based risk score classifier predicts overall survival in hepatocellular carcinoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2500
Description
Immunoglobulin A (IgA) is the major secretory immunoglobulin isotype at mucosal surfaces where it regulates microbial commensalism and excludes luminal factors from contacting intestinal epithelial cells (IEC). IEC endoplasmic reticulum (ER) stress induces a polyreactive IgA response which protects from small intestinal inflammation. IEC ER stress causes expansion and activation of peritoneal B1b cells independent of microbiota and T cells that culminates in increased lamina propria and luminal IgA. Xbp1dIEC mice exhibit IEC ER stress by conditional deletion of X-box-binding protein 1 (XBP1). Here we examine single-cell transcriptomes of peritoneal cavity cells of germ-free Xbp1dIEC mice (KO) compared to littermate controls (WT). Overall design: Single-cell gene expression profiles of peritoneal cavity cells of 10-week-old germ-free Xbp1dIEC and WT mice were generated using a droplet-based system (10X Genomics Chromium).
Publication Title
Epithelial endoplasmic reticulum stress orchestrates a protective IgA response.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 106 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genetic and epigenetic regulation of gene expression in fetal and adult human livers.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 106 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Genome wide expression analysis of 92 adult and 14 fetal liver samples
Publication Title
Genetic and epigenetic regulation of gene expression in fetal and adult human livers.
Sample Metadata Fields
Sex, Specimen part
View Samples