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Comparative gene expression analysis of the rat gastrointestinal tract epithelia

ABSTRACT: Background: The molecular basis of segment specific epithelial functions of the stomach and bowel has not been established. Regionally unique molecular properties of epithelial cells can be identified using cell-specific gene expression in each epithelial region by comparative mRNA analysis. Aim: To describe segment-specific epithelial mRNA content by comparative mRNA analysis of purified epithelial cell suspensions of stomach, small and large bowel. Results: 12% of all annotated genes show segment specific enrichment. The gastric (>3000 genes) and ileal (519 genes) mucosa show the most diverse expression profile. (a) Stomach: The gastric mucosa expresses the machinery for acid secretion, digestive enzyme release, and hormone release by gastric enteroendocrine cells. Associated with acid secretion is a specific set of K+, Cl-, and bicarbonate channels. Novel is a pathway for glucose and fatty acid sensing, iodine and glutamate uptake, and taurine synthesis. Specific sets of transcription factors control epithelial (Barx1, Runx) and enteroendocrine (FoxA2/N4) cell differentiation. (b) Small Bowel: This epithelium expresses genes coding for a unique fructose/glucose uptake and utilization mechanism. Enteroendocrine signalling to the gastric function is present. The upper portion expresses genes for iron uptake, bicarbonate secretion, and detoxification of food contents. Epithelial differentiation is transcriptionally controlled by Meis2/Pdx1 and Onecut 2. Expression of digestive enzymes, lipid/bile acid uptake and utilization increases distally. The ileal epithelium is also involved in innate and acquired immune defence, regulation of motility, and electrolyte and water re-absorption. Transcriptional regulation of enterocyte and goblet cell differentiation is mainly controlled by increasing expression of Cdx1 and 2. (c) Colon: This epithelium is mainly involved in Ca++-, K+, and water re-absorption, fatty acid uptake and sensing, and innate and acquired immune defence. Epithelial differentiation is controlled by Hox transcription factors in addition to Cdx1/2. Conclusion: This regional survey of gene expression by the GI tract epithelium reveals unique epithelial properties, raising several important questions as to the role of the proteins encoded in gut physiology.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE19313 | GEO | 2010/01/03

SECONDARY ACCESSION(S): PRJNA120909

REPOSITORIES: GEO

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Project description:Transcription factor Foxq1 controls mucin gene expression and granule content in mouse stomach surface mucous cells ; Background and Aims: The gastric mucosa provides a stringent epithelial barrier and produces acid and enzymes that initiate digestion. In this regenerating tissue, progenitors differentiate continually into 4 principal specialized cell types, yet underlying mechanisms of differentiation are poorly understood. We identified stomach-restricted expression of the forkhead transcription factor FOXQ1. Methods: We used a combination of genetic, histochemical, ultrastructural and molecular analysis to study gastric cell lineages with respect to FOXQ1. Results: Within the developing and adult gastrointestinal tract, Foxq1 mRNA is restricted to the stomach, expressed prominently in foveolar (pit) cells, the abundant mucin-producing cells that line the mucosal surface, and required for their complete differentiation. Mice carrying Foxq1 coding mutations show virtual absence of mRNA and protein for the backbone of the predominant stomach mucin, MUC5AC. These observations correspond to a paucity of foveolar-cell secretory vesicles and notable loss of stomach but not intestinal mucus. Transcriptional profiling identified a surprisingly restricted set of genes with altered expression in Foxq1 mutant stomachs. MUC5AC is a highly tissue-restricted product that similarly depends on FOXQ1 in its other major site of expression, conjunctival goblet cells. Conclusions: Taken together, these observations imply that promotion of gastric MUC5AC synthesis is a primary, cell-autonomous function of FOXQ1. This study is the first to implicate a transcription factor in terminal differentiation of foveolar cells and begins to define the requirements to assemble highly specialized organelles and cells in the gastric mucosa. DOI: 10.1053/j.gastro.2008.04.019 Experiment Overall Design: RNA from stomach antrum from 2 of each Satin, Beige, and BL6 mice were compared using microarray analysis.

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Comparative gene expression analysis of the rat gastrointestinal tract epithelia

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