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HNF4A regulation of transcription profiles in the mouse intestinal epithelial cells

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

PROVIDER: PRJNA819968 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR18482532_1.fastq.gz	Fastqsanger.gz
	SRR18482532_2.fastq.gz	Fastqsanger.gz
	SRR18482533_1.fastq.gz	Fastqsanger.gz
	SRR18482533_2.fastq.gz	Fastqsanger.gz
	SRR18482534_1.fastq.gz	Fastqsanger.gz

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HNF4A regulation of transcription profiles in the mouse cecal epithelial cells

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.

2022-06-30 | GSE199415 | GEO

HNF4A regulation of transcription profiles in the mouse ileal and colonic epithelial cells

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.

2022-06-30 | GSE199416 | GEO

HNF4A regulation of transcription profiles in the mouse cecal epithelial cells

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

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HNF4A regulation of transcription profiles in the mouse ileal and colonic epithelial cells

Project description:HNF4A regulation of transcription profiles in the mouse ileal and colonic epithelial cells

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HNF4A intestinal epithelial conditional loss incidence on jejunum expression from mice fed a HFD.

Project description:HNF4A encodes a nuclear receptor required for the development of the intestine and involved in the homeostasis maintenance of intestinal epithelial cells during the adulthood. Also strongly related to the hepatic lipid metabolism, little was known about its metabolic relevance from the intestine when challenged by a high fat diet. We used microarrays to detail the global programme of jejunal gene expression depending on HNF4α and influenced by HFD.

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HNF4a acts as upstream functional regulator of intestinal Wnt3 and Paneth cell fate

Project description:Maturation of Paneth cells depends on canonical Wnt signaling, but few transcriptional regulators have been identified to this end. We showed that HNF4a plays a non-redundant and crucial role in supporting the growth and survival of small intestinal epithelial cultures when cultured ex vivo as organoids. Transcriptomic analyses revealed an autosomal function of HNF4a in Wnt3 transcriptional regulation and Paneth cell differentiation. We showed that Wnt3a supplementation reversed cell death and transcriptional changes caused by the deletion of Hnf4a in jejunal organoids.

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HNF4a acts as upstream functional regulator of intestinal Wnt3 and Paneth cell fate [RNA-seq]

2022-12-01 | GSE171657 | GEO

HNF4A regulation of transcription profiles in the mouse intestinal epithelial cells

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-06-30 | GSE199417 | GEO

RIME Analysis of HNF4A binding partners in the intestinal epithelium

Project description:The mechanisms driving gene expression changes during intestinal differentiation are unclear. Our studies have shown differential recruitment and occupancy of Pol II to be a major driver of these gene expression changes. Additionally, we have identified the transcription factor HNF4 as a key player in shaping this phenomenon. To gain insights into the protein-based mechanisms underlying HNF4-mediated Pol II recruitment, we performed RIME (Rapid Immunoprecipitation Mass Spectrometry of Endogenous proteins) using anti-HNF4A antibodies in primary mouse epithelium.

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Project description:To determine whether the intestine-restricted transcription factor (TF) CDX2 functionally interacts with the endoderm-wide TF HNF4A, we crossed tissue-specific conditional Cdx2 and Hnf4a knockout mice to generate compound mutant mice. We used RNA-sequencing to profile gene expression changes in compound mutant mice compared to control mice. The compound mutant mice had a significantly worse phenotype than either single mutant, and gene expression was significantly perturbed in compound mutants compared to control mice. Total RNA isolated from control and compound mutant (Hnf4a-del;Cdx2-del) jejunal mouse intestinal epithelium was prepared for sequencing using the TruSeq RNA Sample Preparation Kit (Illumina) according to the manufacturer's instructions. 75-base-pair single-end reads were sequenced on an Illumina NextSeq 500 instrument. The data include 2 independent biological replicates per genotype.

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