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Single nuclei transcriptomics of colonic epithelium

ABSTRACT: FOXA1 and FOXA2 are essentail transcription factors for proper gut development. In adults, they play a role in the differentiation of intestinal secretory cells and were also reporeted to directly activate Muc2 transcription. Here we show that deletion of Foxa1 and Foxa2 in mouse intestinal epithelium leads to a downregulation of glycosylation genes in the colon and to a massive change of the colonic surface glycans, which in turn leads to dysbiosis and to inflammatory bowel disease. In order to associate this phenotype with a specific colonic lineage, we generated cell specific gene sets by performing single nuclei RNA-seq on colonic tissue from control mice. Gene set enrichment analysis demonstrated major changes in Goblet cell genes following Foxa1/2 deletion, including glycosylation genes. However, other lineages were also affected. We concluded that vertebrates shape a favorable microbiome by establishing a glycocalyx to nurture specific bacterial taxa through control of the epithelial glycosylation program by the FoxA transcription factors.

ORGANISM(S): Mus musculus

PROVIDER: GSE263631 | GEO | 2024/05/14

REPOSITORIES: GEO

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Transcriptome of Foxa1/Foxa2-deficient colon [RNA]

Project description:FOXA1 and FOXA2 are essentail transcription factors for proper gut development. In adults, they have a role in the differentiation of intestinal secretory cell lineages and were also reporeted to directly activate Muc2 transcription. Here we show that deletion of Foxa1 and Foxa2 in mouse intestinal epithelium leads to a downregulation of glycosylation genes in the colon and to a massive change of the colonic surface glycans. In turn, the microbiome composition shifts dramatically and spontaneous inflammatory bowel disease ensued. We conclude that vertebrates shape a favorable microbiome by establishing a glycocalyx to nurture specific bacterial taxa through control of the epithelial glycosylation program by the FoxA transcription factors.

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