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HNF4A regulation of transcription profiles in the mouse intestinal epithelial cells

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE199417 | GEO | 2022/06/30

REPOSITORIES: GEO

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HNF4A regulation of transcription profiles in the mouse intestinal epithelial cells

Project description:HNF4A regulation of transcription profiles in the mouse intestinal epithelial cells

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Project description:Purpose: HNF4A is a highly conserved nuclear receptor that has been associated with inflammatory bowel diseases. The goal of this study is to determine transcriptional regulation by HNF4A in the cecal IECs.. Methods: Intestinal epithelial cells (IECs) were sorted from the ceca of young adult WT and HNF4A IEC-specific KO mice and sequenced for transcriptome. Differentially expressed genes comparing the WT and HNF4A IEC-KO were determined. Results: Epithelial HNF4A regulates expression of hundreds of genes. HNF4A is particularly required for the expression of a set of immune signaling molecules that are critical for the IEC-intrapithelial lymphocyte crosstalk. Those molecules include members of the butyrophilin-like molecules (Btnl1 and Btnl6) and MHC-I like molecule H2-T3 etc. Expression of the immune signaling molecules was validated by qPCR. Further comparison with HNF4A ChIP-seq datasets confirmed that those genes are also direct HNF4A targets.

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Project description:Purpose: HNF4A is a highly conserved nuclear receptor that has been associated with inflammatory bowel diseases. The goal of this study is to determine and compare transcriptional regulation by HNF4A in the small intestine and large intestine in mice. Methods: Intestinal epithelial cells (IECs) were flow sorted from the ileum and colon of WT and HNF4A IEC-specific KO mice at 21~22 days old and sequenced for transcriptome. Differentially expressed genes in the illeum and colon respectively comparing the WT and HNF4A IEC-KO were determined. Results: HNF4A regulates expression of hundreds of genes in both ileal and colonic IECs. However, many of the DE genes and the magnitude of changes are location specific. In general, a more significant dependancy on HNF4A is found in the colon. HNF4A is particularly required for the expression of a set of immune signaling molecules that are critical for the IEC-intrapithelial lymphocyte crosstalk. Those molecules include members of the butyrophilin-like molecules (Btnl1, Btnl2, Btnl4, and Btnl6) and MHC-I like molecule H2-T3 etc. Expression of the immune signaling molecules was validated by qPCR. Further comparison with HNF4A ChIP-seq datasets and validation with ChIP-qPCR confirmed that those genes are also direct HNF4A targets.

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