How form follows functional genomics: gene expression profiling gastric epithelial cells with a particular discourse on the parietal cell

Abstract

The cellular composition and morphology of the stomach epithelium have been described in detail; however, the molecular mechanisms that regulate the differentiation of the various cell lineages as well as the function of mature gastric cells are far less clear. Recently, dissection of the molecular anatomy of the stomach has been boosted by the advent of functional genomics, which allows investigators to determine patterns of gene expression across virtually the entire cellular transcriptome. In this review, we discuss the impact of functional genomic studies on the understanding of gastric epithelial physiology. We show how functional genomic studies have uncovered genes that are useful as new cell lineage-specific markers of differentiation and provide new insights into cell physiology. For example, vascular endothelial growth factor B (Vegfb) has been identified as a parietal cell-specific marker that may allow parietal cells to regulate the mucosal vascular network. We also discuss how functional genomics has identified aberrantly expressed genes in disease states. Human epididymis 4 (HE4), for example, was recently identified as a metaplasia-induced gene product in mice based on microarray analysis. Finally, we will examine how analysis of higher-order patterns of gene expression can go beyond simply identifying individual genes to show how cells work as integrated systems. Specifically, we show how application of a Gene Ontology (GO) analysis of gene expression patterns from multiple tissues identifies the gastric parietal cell as an outlier, unlike other differentiated cell lineages in the stomach or elsewhere in the body.