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GSE23040
Mus musculus
6 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Although hepatocyte-nuclear-factor-1 (Hnf1) 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 Hnf1 on the maintenance of adult small intestinal epithelial functions.
Publication Title
Loss of hepatocyte-nuclear-factor-1alpha impacts on adult mouse intestinal epithelial cell growth and cell lineages differentiation.
Sample Metadata Fields
Age, Specimen part, Disease
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Hepatocyte-nuclear-factor-4 (Hnf4) is a transcription factor that controls epithelial cell polarity and maturation during embryogenesis. Hnf4 conditional deletion during post-natal development results in minor consequences on intestinal epithelium integrity but promotes activation of the Wnt/-catenin pathway. Here we show that Hnf4 does not act as a tumor suppressor gene but is crucial to promote gut tumorigenesis in mice. Polyp multiplicity in ApcMin mice that lacks Hnf4 is suppressed in comparison to littermate ApcMin controls. Analysis of microarray gene expression profiles from mice lacking Hnf4 in the intestinal epithelium identifies its novel function in regulating the expression of reactive oxygen species (ROS) detoxifying genes. This role is supported with the demonstration that HNF4 is functionally involved in the protection against spontaneous and 5-fluorouracil chemotherapy-induced production of intracellular ROS in colorectal cancer cell lines. The analysis of a colorectal cancer patient cohort establishes that HNF4 is significantly up-regulated at both gene transcript and protein levels in tumors relative to adjacent benign epithelial resections. Several genes involved in ROS neutralization are also up-regulated in correlation with HNF4 expression. All together, the findings point to the nuclear receptor HNF4 as a potential therapeutic target to eradicate aberrant epithelial cell resistance to ROS production during intestinal tumorigenesis.
Publication Title
Hepatocyte nuclear factor-4alpha promotes gut neoplasia in mice and protects against the production of reactive oxygen species.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Background & Aims: HNF4 is an important transcriptional regulator of hepatocyte and pancreatic function. Hnf4 deletion is embryonically lethal with severe defects in visceral endoderm formation, liver maturation and colon development. However, the precise role of this transcription factor in maintaining homeostasis of the adult intestine remains unclear. Herein, we aimed to elucidate the adult intestinal functions of Hnf4. Methods: A conditional intestinal epithelial Hnf4 knockout mouse was generated. Histological abnormality of the colonic mucosa was assessed by immunodetection and Western. Changes in global gene expression and biological network were analyzed. Results: Hnf4 intestine null mice developed normally until reaching young adulthood. Crypt distortion became apparent in the Hnf4 null colon at 3 months of age followed by focal areas of crypt dropout, increased immune cell infiltrates, crypt hyperplasia and early signs of polyposis later in life. A gene profiling analysis identified cell death and cell cycle related to cancer as the most significant sets of genes altered in the Hnf4 colon null mice. Expression levels of the tight junction proteins claudin 4, 8 and 15 were altered early in the colon epithelium of Hnf4 mutants and correlated with increased barrier permeability to a molecular tracer that does not normally penetrate normal mucosa. Conclusion: These observations support a functional role for Hnf4 in protecting the colonic mucosa against the initiation of the changes resembling inflammatory bowel diseases and polyp formation.
Publication Title
Loss of hepatocyte-nuclear-factor-4alpha affects colonic ion transport and causes chronic inflammation resembling inflammatory bowel disease in mice.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 16 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
The inflammatory response of preterm infants' intestine underlines its inability to respond to hemodynamic stress, microbes and nutrients. Recent evidence suggests that exogenous epidermal growth factor (EGF) exerts a therapeutic influence on neonatal enteropathies. However, the molecular mechanisms underlying the beneficial effects of EGF remain to be clarified. The purpose of this study was to evaluate the impact of EGF on the gene expression profiles of the developing human small and large intestine at mid-gestation in serum-free organ cultures using Illumina microarrays.
Publication Title
Anti-inflammatory effects of epidermal growth factor on the immature human intestine.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 15 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Transcriptional profiling after inhibition of cellulose synthesis by thaxtomin A and isoxaben in Arabidopsis thaliana suspension cells
Publication Title
Transcriptional profiling in response to inhibition of cellulose synthesis by thaxtomin A and isoxaben in Arabidopsis thaliana suspension cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
LRH-1 governs vital transcriptional programs in endocrine-sensitive and -resistant breast cancer cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Tumor characteristics are decisive in the determination of treatment strategy for breast cancer patients. Patients with estrogen receptor- (ER) positive breast cancer can benefit from long-term hormonal treatment. Nonetheless, the majority of patients will develop resistance to these therapies. Here, we investigated the role of the liver receptor homolog-1 (LRH-1, NR5A2) in anti-estrogen (AE) sensitive and resistant breast cancer cells. We identified genome-wide LRH-1 binding sites using ChIP-seq, uncovering preferential binding to regions distal to transcriptional start sites (TSS). We further characterized these LRH-1 binding sites by integrating overlapping layers of specific chromatin marks, revealing that many LRH-1 binding sites are active and could be involved in long-range enhancer-promoter looping. Combined with transcriptome analysis of LRH-1 depleted cells, these results show that LRH-1 regulates specific subsets of genes involved in cell proliferation in AE-sensitive and AE-resistant breast cancer cells. Furthermore, the LRH-1 transcriptional program is highly associated with signature of poor outcome breast cancer tumors in vivo. Herein report the genome-wide location and molecular function of LRH-1 in breast cancer cells and reveal its therapeutic potential for the treatment of breast cancers, notably for tumors resistant to treatments currently used in therapies.
Publication Title
LRH-1 governs vital transcriptional programs in endocrine-sensitive and -resistant breast cancer cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Transcriptional profiling of small intestinal explants cultured in the absence or in the presence of Ibuprofen (100 M).
Publication Title
Impaired antimicrobial response and mucosal protection induced by ibuprofen in the immature human intestine.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Estrogen-Related Receptor alpha (ERR) is a nuclear receptor that acts principally as a regulator of metabolism processes particularly in tissues subjected to high-energy demand. Besides its implication in energy metabolism and mitochondrial biogenesis, ERR was recently associated with tumorigenesis. Notably, increased expression of ERR was noted in different cancerous tissues as breast, ovary and colon. However, supplemental studies are required to better understand the role of ERR in colon carcinoma.
Publication Title
ERRα metabolic nuclear receptor controls growth of colon cancer cells.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
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.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples