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GSE16440
Mus musculus, Helicobacter pylori
60 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Response of gastric epithelial progenitors to Helicobacter pylori Isolates obtained from Swedish patients with chronic atrophic gastritis.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples- Mus musculus
- 60 Downloadable Samples
Description
Helicobacter pylori infection is associated with development of gastric adenocarcinoma in a subset of infected humans, especially those that develop an antecedent condition, chronic atrophic gastritis (ChAG) characterized by loss of acid-producing parietal cells. Studies in a gnotobiotic transgenic mouse model of ChAG, with an engineered ablation of parietal cells and an associated expansion of gastric epithelial progenitors (GEPs), have shown that a subset of GEPs is able to harbor intracellular collections of H. pylori. To better understand H. pyloris adaptation to ChAG, we sequenced the genomes of 24 isolates, obtained from 6 individuals, each sampled over a 4-year interval, as they maintained normal gastric histology, or progressed from normal histology to ChAG, or experienced worsening ChAG, or proceeded from ChAG to cancer. Analyses of gene content and single nucleotide polymorphisms (SNPs) demonstrated that H. pylori populations within study participants were largely clonal, and remarkably stable over the 4-year interval, regardless of disease state. Because they exhibited such broad inter-host variation (38.64.7 SNPs/1000bp of genome), and did not cluster according to host pathology, we sought to identify common functional properties by performing GeneChip studies of the responses of a cultured mouse gastric stem cell-like line (mGEPs) to infection with sequenced strains. The results yielded a shared 695-member set of genes differentially expressed after infection with ChAG-associated, but not normal or heat killed strains: 434 of these genes were also represented in dataset of responses to the cancer-associated strain. Ingenuity Pathway Analysis revealed that ChAG- and ChAG/cancer- associated responses were significantly enriched in genes associated with tumorigenesis in general, and gastric carcinogenesis in specific cases. Whole genome transcriptional profiling of a sequenced ChAG strain during mGEP infection disclosed a set of responses that included upregulation of hopZ, an adhesin belonging to a family of outer membrane proteins. Expression profiles of wild-type and hopZ strains revealed a number of pH-regulated genes affected by loss of HopZ, including HopP which binds sialylated glycans produced by GEPs in vivo. Genetic inactivation of hopZ produces a fitness defect in gnotobiotic transgenic mice but not their wild-type littermates. This study illustrates an approach for identifying GEP responses specific to ChAG, and bacterial genes important for survival in a gastric ecosystem that lacks parietal cells.
Publication Title
Response of gastric epithelial progenitors to Helicobacter pylori Isolates obtained from Swedish patients with chronic atrophic gastritis.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples- Mus musculus
- 26 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Zbtb46 expression distinguishes classical dendritic cells and their committed progenitors from other immune lineages.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 15 Downloadable Samples
Description
Analysis of genes induced in DC precursors and in BM cells and monocytes treated with GM-CSF
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
Description
The goal was to determine how IL-12 affects gene expression by murine CTL.
Publication Title
IL-12 enhances CTL synapse formation and induces self-reactivity.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
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.
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 18 Downloadable Samples
Description
Helicobacter pylori clinical isolates can establish themselves in gastric epithelial stem cells and this interaction may have implications for gastric tumorigenesis. Mouse gastric epithelial progenitor cells (mGEPs) and non-progenitor gastric epithelial cells (npGECs) were infected for 24hrs with Helicobacter pylori clinical isolates Kx1 and Kx2. Kx1 was isolated from a patient with chronic atrophic gastritis (ChAG) and Kx2 from the same patient 4 years later, when he progressed to gastric adenocarcinoma.
Publication Title
Helicobacter pylori evolution during progression from chronic atrophic gastritis to gastric cancer and its impact on gastric stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 16 Downloadable Samples
Description
The purpose of this study was to determine the effect of peripheral (IV) administration of APP antisense on hippocampal gene expression as well as on learning and memory as measured by T-maze in adult male mice aged 12 months. The APP antisense treatment reversed learning and memory deficits and altered the expression of 944 hippocampal genes, which are involved in a coordinated set of signaling pathways. Expression and pathway findings were verified at the protein and functional (phosphorylation) levels.
Publication Title
No associated publication
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
Description
This study examined the effects of castration and testosterone replacement on global differential gene transcription in the gastrocnemius muscle (m.Gas) in young adult mice over 14-days.
Publication Title
Testosterone modulates gene expression pathways regulating nutrient accumulation, glucose metabolism and protein turnover in mouse skeletal muscle.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 33 Downloadable Samples
Description
The mature CNS contains PDGFRA+ oligodendrocyte progenitor cells (OPC) which may remain quiescent, proliferate, or differentiate into oligodendrocytes. In human gliomas, rapidly proliferating Olig2+ cells resembling OPCs are frequently observed. We sought to identify, in vivo, candidate pathways uniquely required for OPC differentiation or quiescence. Using the bacTRAP methodology, we generated and analyzed mouse lines for translational profiling the major cells types (including OPCs), in the normal mouse brain. We then profiled oligodendoglial (Olig2+) cells from a mouse model of Pdgf-driven glioma. This analysis confirmed that Olig2+ tumor cells are most similar to OPCs, yet, it identified differences in key progenitor genes - candidates for promotion of differentiation or quiescence.
Publication Title
Candidate pathways for promoting differentiation or quiescence of oligodendrocyte progenitor-like cells in glioma.
Sample Metadata Fields
Specimen part
View Samples