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Series GSE16390 Query DataSets for GSE16390
Status Public on Oct 27, 2009
Title Response of gastric epithelial progenitors to H. pylori isolates from Swedish patients with chronic atrophic gastritis 1
Organism Mus musculus
Experiment type Expression profiling by array
Summary 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. pylori’s 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 (38.6±4.7 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 hopZΔ 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.
 
Overall design mGEPs and npGECs were seeded and grown to 70% confluency in RPMI1640 medium supplemented with 10% FBS before being infected with H. pylori strains that had been grown to log phase. After 24h, media and non-attached bacteria were washed off and the cells harvested by trypsinization. RNA was prepared from triplicate cultures of mGEP or npGECs cells.
 
Contributor(s) Giannakis M, Gordon JI
Citation(s) 19723631
Submission date Jun 02, 2009
Last update date Feb 11, 2019
Contact name Jeremiah J Faith
E-mail faithj@wustl.edu
Organization name Washington University in St. Louis
Street address Campus Box 8510
City Saint Louis
State/province MO
ZIP/Postal code 63108
Country USA
 
Platforms (1)
GPL1261 [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
Samples (60)
GSM411428 Mouse gastric epithelial progenitor cells, uninfected, replicate 1
GSM411429 Mouse gastric epithelial progenitor cells, uninfected, replicate 2
GSM411430 Mouse gastric epithelial progenitor cells, uninfected, replicate 3
This SubSeries is part of SuperSeries:
GSE16440 Response of gastric epithelial progenitors to H. pylori isolates from Swedish patients with chronic atrophic gastritis
Relations
BioProject PRJNA122883

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Supplementary file Size Download File type/resource
GSE16390_RAW.tar 348.7 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

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