Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA280810 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR1964296.fastq.gz | Fastqsanger.gz | |||
| SRR1964297.fastq.gz | Fastqsanger.gz | |||
| SRR1964298.fastq.gz | Fastqsanger.gz | |||
| SRR1964299.fastq.gz | Fastqsanger.gz |
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Project description:Background and Aims: Hepatocyte nuclear factor 1 (HNF1) transcription factors direct tissue specific gene regulation in liver, pancreas and kidney and are associated with diabetes. Here we investigate the transcriptional network governed by HNF1 in an intestinal epithelial cell line. Methods: Chromatin immunoprecipitation followed by direct sequencing (ChIP-seq) was used to identify HNF1 binding sites genome-wide. Direct targets of HNF1 were validated using conventional ChIP assays. siRNA-mediated depletion of HNF1 followed by RT-qPCR further confirmed target genes. The effect of HNF1 reduction on glucose uptake was measured by fluorescence activated cell sorting (FACS) following treatment of intestinal epithelial cells with 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-d-glucose (2-NBDG, a fluorescent glucose mimic). Results: HNF1 controls multiple pathways that are critical for intestinal epithelial cell function, including properties of the cell membrane, cellular response to hormones, and regulation of biosynthetic processes. Approximately 50% of HNF1 binding sites are also occupied by hepatocyte nuclear factor 4A (HNF4A), caudal type homeobox 2 (CDX2), and forkhead box A2 (FOXA2). Depletion of HNF1 increases FOXA2 abundance and decreases levels of CDX2. Moreover, loss of HNF1 inhibits glucose uptake by the intestinal epithelial cell line. Conclusions: These data show that HNF1 plays a critical role in regulating intestinal epithelial cell functions including glucose absorption. HNF1 interacts with other tissue-specific transcription factors to regulate differentiated properties of these cells.
2016-10-09 | GSE67740 | GEO
Project description:Although hepatocyte-nuclear-factor-1α (Hnf1α) is crucial for pancreas and liver functions, it is believed to play a limited functional role for intestinal epithelial functions. The aim of this study was to assess the consequences of abrogating Hnf1α on the maintenance of adult small intestinal epithelial functions. Methodology/Principal Findings An Hnf1α knockout mouse model was used. Assessment of histological abnormalities, crypt epithelial cell proliferation, epithelial barrier, glucose transport and signalling pathways were measured in these animals. Changes in global gene expression were also analyzed. Mice lacking Hnf1α displayed increased crypt proliferation and intestinalomegaly as well as a disturbance of intestinal epithelial cell lineages production during adult life. This phenotype was associated with a decrease of the mucosal barrier function and lumen-to-blood glucose delivery. The mammalian target of rapamycin (mTOR) signalling pathway was found to be overly activated in the small intestine of adult Hnf1α mutant mice. The intestinal epithelium of Hnf1α null mice displayed a reduction of the enteroendocrine cell population. An impact was also observed on proper Paneth cell differentiation with abnormalities in the granule exocytosis pathway. Conclusions/Significance Together, these results unravel a functional role for Hnf1α in regulating adult intestinal growth and sustaining the functions of intestinal epithelial cell lineages. HNF1alpha was knocked out. A total of 3 control and 3 mutant littermate individuals were sacrificed at 4 months of age. The jejunum was harvested and total RNA was isolated from each individual. Each RNA sample was independently used to generate probes to screen Affymetrix chips.
2011-01-01 | E-GEOD-23040 | biostudies-arrayexpress
Project description:Although hepatocyte-nuclear-factor-1α (Hnf1α) is crucial for pancreas and liver functions, it is believed to play a limited functional role for intestinal epithelial functions. The aim of this study was to assess the consequences of abrogating Hnf1α on the maintenance of adult small intestinal epithelial functions. Methodology/Principal Findings An Hnf1α knockout mouse model was used. Assessment of histological abnormalities, crypt epithelial cell proliferation, epithelial barrier, glucose transport and signalling pathways were measured in these animals. Changes in global gene expression were also analyzed. Mice lacking Hnf1α displayed increased crypt proliferation and intestinalomegaly as well as a disturbance of intestinal epithelial cell lineages production during adult life. This phenotype was associated with a decrease of the mucosal barrier function and lumen-to-blood glucose delivery. The mammalian target of rapamycin (mTOR) signalling pathway was found to be overly activated in the small intestine of adult Hnf1α mutant mice. The intestinal epithelium of Hnf1α null mice displayed a reduction of the enteroendocrine cell population. An impact was also observed on proper Paneth cell differentiation with abnormalities in the granule exocytosis pathway. Conclusions/Significance Together, these results unravel a functional role for Hnf1α in regulating adult intestinal growth and sustaining the functions of intestinal epithelial cell lineages.
2011-01-01 | GSE23040 | GEO
Project description:Microbiota regulate intestinal epithelial gene expression by suppressing the transcription factor Hepatocyte nuclear factor 4 alpha
| PRJNA354702 | ENA
Project description:The interferon-inducible transcription factor STAT1 is a tumor suppressor in various malignancies. We investigated STAT1 functions in intestinal tumorigenesis of ApcMin mice. Surprisingly, loss of STAT1 in intestinal epithelial cells (STAT1ΔIEC) interfered with ApcMin induced intestinal tumor formation and tumor progression. RNASeq data demonstrated reduced expression of Indoleamine-2,3-dioxygenase-1 (IDO1) in STAT1ΔIEC ApcMin tumors. IDO1 is implicated in synthesis of kynurenine, a metabolite that induces ß-Catenin nuclear localisation and suppresses anti-tumor immune responses.
2020-04-05 | E-MTAB-5083 | biostudies-arrayexpress
Project description:During mammalian development, liver differentiation is driven by signals which converge on multiple transcription factor networks. The hepatocyte nuclear factor signalling network is known to be essential for hepatocyte specification and maintenance. In these studies we demonstrate that nuclear HNF4a is essential for hepatic progenitor specification and the introduction of point mutations in HNF4a’s SUMO consensus motif leads to disrupted hepatocyte specification and maturation.
2019-10-31 | E-MTAB-7951 | biostudies-arrayexpress
Project description:Plasticity of differentiated cells has been proved by nuclear transfer, induced pluripotent cells and transdifferentiation. Here we show that by transduction of 3 factors (Hnf1alpha, Gata4, and Foxa3) and p19Arf inactivation, tail-tip fibroblasts can be converted to hepatocyte-like (iHep) cells, expressing hepatocyte marker genes, and acquiring many mature hepatocyte functions in vitro and in vivo. p19Arf-null TTFs were tranfected with 3 liver enriched transcription factors, then changed to modified Block's medium. To enrich iHep cells, epithelial cells were enriched by partial trypsin digestion.
2011-05-11 | E-GEOD-23635 | biostudies-arrayexpress
Project description:Identifying Hepatocyte Growth Factor dose response functions in Madin-Darby Canine Kidney Epithelial Cells
| PRJEB14919 | ENA
Project description:Microbiota regulate intestinal epithelial gene expression by suppressing the transcription factor Hepatocyte nuclear factor 4 alpha (zebrafish RNA-seq)
| PRJNA354631 | ENA
Project description:Post-translational modification of proteins has been shown to control different aspects of protein biology. We have previously implicated a SUMO consensus motif in HNF4alpha’s carboxylic terminus as an important regulator of protein biology during stem cell differentiation. In this study, we have generated deletion and point mutants of HNF4alpha to precisely study the role of protein domains during hepatocyte specification. During mammalian development, liver differentiation is driven by signals which converge on multiple transcription factor networks. The hepatocyte nuclear factor signalling network is known to be essential for hepatocyte specification and maintenance. In these studies we demonstrate that nuclear HNF4 is essential for hepatic progenitor specification and the introduction of point mutations in HNF4alpha’s SUMO consensus motif leads to disrupted hepatocyte specification and maturation. Taking a multi-omics approach, we identified key deficiencies in cell biology which included; dysfunctional cell metabolism, cell adhesion, tricarboxylic acid cycle flux, mRNA transport and processing. In summary, the combination of genome editing and multi-omics analyses have provided new insight into the diverse functions of HNF4alphaprotein during human hepatocyte specification and maturation.
2019-06-17 | PXD013737 | Pride