HNF4A regulation of transcription profiles in the mouse cecal epithelial cells

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. Overall design: RNA profiling of cecal IECs from cohoused littermated controlled 8-week-old WT (Hnf4a fl/fl) and HNF4A IEC-specific KO (Hnf4a fl/fl Villin-Cre) mice. 3 biological replicates for each group.