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A Time-resolved Multi-omic Atlas of the Developing Mouse Stomach

ABSTRACT: The mouse stomach secrets digestive enzymes and stomach acid, and plays a key role in food digestion. While there are a few studies on the morphological changes during the stomach development, a comprehensive, systematic omics study is still missing. Here, we present a comprehensive, temporal proteome atlas of the mouse stomach by sequential mapping stomach tissues at multiple developmental stages. The quantitative analysis of 12,108 gene products provides coverage sufficient to observe the protein dynamics of the developing stomach. The whole process of stomach development can be roughly divided into three phases according to changes of RNAs or proteins. The molecular functions of protein modules pinpoint the gain of stomach functions at the longitudinal scale. Dissection of 8 key signaling pathways identified master regulators in governing stomach development and gastric cancer. Remarkably, many proteins differentially expressed in stomach development are also significantly overexpressed in diffuse-type gastric cancer, suggesting a close correlation between development and tumorigenesis. The transcriptome of the developing stomach reveals functionally important isoforms relevant to development. When combined with the proteomes, several functionally unannotated novel splicing junction transcripts were identified and validated at the peptide level. Overall, our study provides a valuable resource to understand stomach development and its connection to gastric cancer.

ORGANISM(S): Mus musculus

PROVIDER: GSE118083 | GEO | 2018/08/04

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.