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GSE50621
Mus musculus
29 Downloadable Samples
Illumina MouseRef-8 v2.0 expression beadchip
Description
Expression analyses comparing c-Fos expressing keratinocytes vs non-expressing controls.
Publication Title
Inflammation-mediated skin tumorigenesis induced by epidermal c-Fos.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Mus musculus
- 16 Downloadable Samples
Illumina HiSeq 2000, Illumina Genome Analyzer IIx
Description
c-Fos, a member of the stress-activated Activator Protein 1 (AP-1) transcription factor family, is expressed in human hepatocellular cancer (HCC). Using genetically engineered mouse models (GEMMs) we show that hepatocyte-specific expression of c-Fos leads to a proliferative, de-differentiated phenotype, whereas hepatocyte-specific deletion of c-Fos protects against diethylnitrosamine (DEN)-induced liver cancer. Furthermore, c-Fos-expressing livers resemble human HCCs based on expression profiles. In the present RNA seq, we intend to analyze the transcriptomic profile of livers at 2 and 4 mo hepatocyte-specific c-Fos expression compared to the corresponding age-matched control mice. Moreover, we analyzed livers of mice with hepatocyte-specific deletion c-Fos at 48h after DEN treatment compared to identically treated control mice. Overall design: The general idea was to analyze the transcriptomic profile of hepatocyte-specific c-Fos over-expressing livers at 2 and 4 mo expression. Hereby, a hepatocyte-specific doxycycline (Dox)-switchable mouse model was (LAP-tTA; col1a1:Tet-O-fosFlag) was generated and c-Fos expression was induced at the age of 3 weeks by removal of doxycycline. Each sample LaptTA-fos-MUT represents an individual hepatocyte-specific c-fos expressing mouse at the indicated time-point and the corresponding identically treated control mouse LaptTA-fos-CO. Moreover, the transcriptomic profile of livers with hepatocyte-specific deletion of c-Fos at 48h after diethylnitrosamine (DEN)-induced liver cancer initiation was analyzed. For hepatocyte-specific knock-out of c-Fos, mice with conditional alleles of c-fos and the Alfp-Cre transgene were used. Control mice only carried the Alfp-Cre transgene. At the age of 8 weeks these mice were injected with 100mg/kg DEN. Each sample AlfpCre-fos-MUT_DEN represents an individual hepatocyte-specific c-fos knock-out mouse 48h after DEN and the identically treated control mouse AlfpCre-fos-CO-Cre+_DEN.
Publication Title
Liver carcinogenesis by FOS-dependent inflammation and cholesterol dysregulation.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The mitogen-activated protein kinase (MAPK) p38alpha controls inflammatory responses and cell proliferation. Using mice carrying conditional p38alpha alleles, we investigated its function in postnatal development and tumorigenesis. When p38alpha is specifically deleted in the mouse embryo, fetuses develop to term but die shortly after birth, likely due to lung dysfunction. Fetal hematopoietic cells and embryonic fibroblasts deficient in p38alpha display increased proliferation, resulting from sustained activation of the c-Jun N-terminal kinase (JNK)/c-Jun pathway. Importantly, in chemical-induced liver cancer development, mice with liver-specific deletion of p38alpha show enhanced hepatocyte proliferation and tumor development that also correlates with JNK/c-Jun upregulation. Furthermore, increased proliferation of p38alpha-deficient hepatocytes and tumor cells is suppressed by inactivation of JNK or c-Jun. These results reveal a novel mechanism whereby p38alpha negatively regulates cell proliferation through antagonizing the JNK/c-Jun pathway in multiple cell types and in liver cancer development.
Publication Title
p38alpha suppresses normal and cancer cell proliferation by antagonizing the JNK-c-Jun pathway.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 21 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
RNA-seq was performed using the RNA extracted from the bottom half of right lobe of mouse livers. Mice fall into two groups, mutant group which express ectopic hURI and their control littermates which do not express hURI. Two time points were considered in the study, 1-week-old mice, expressing hURI since 1 week (n =3, 4 for control and mutant, respectively) and 8-week-old mice expressing hURI since 8 week (n= 4, 3 for control and mutant, respectively), as hURI is expressed since conception. Overall design: Determination of differentially expressed transcripts over two time points (1 week and 8 weeks) in mouse livers expressing hURI (1 week and 8 weeks).
Publication Title
Inhibition of de novo NAD(+) synthesis by oncogenic URI causes liver tumorigenesis through DNA damage.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 24 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Genome-wide analysis of GBM-derived brain tumor stem cells-like (BTSCs) collected at the Freiburg Medical Center and UAB (JX6)
Publication Title
NF1 regulates mesenchymal glioblastoma plasticity and aggressiveness through the AP-1 transcription factor FOSL1.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
Background & Aims: Perturbations in pancreatic ductal bicarbonate secretion often result in chronic pancreatitis. Although the physiological mechanism of ductal secretion is known, its transcriptional control is not well characterized. Here, we investigate the role of the transcription factor Hematopoietically-expressed homeobox protein (Hhex) in pancreatic secretion and pancreatitis. Methods: We derived mice with pancreas-specific, Cre-mediated Hhex gene ablation to determine the requirement of Hhex in the pancreatic duct in early life and in adult stages. Histological and immunostaining analyses were used to detect the presence of pathology. Pancreatic primary ductal cells (PDCs) were isolated to discover differentially expressed transcripts upon acute Hhex ablation. Results: Hhex protein was detected throughout the embryonic and adult ductal trees. Ablation of Hhex in pancreatic progenitors resulted in postnatal ductal ectasia associated with acinar-to-ductal metaplasia, a progressive phenotype that ultimately resulted in chronic pancreatitis. Hhex ablation in adult mice, however, did not cause any detectable pathology. Ductal ectasia did not result from perturbations in primary cilia, but was consistent with the effects of primary ductal hypertension. RNA-seq analysis of Hhex-ablated PDCs indicated the G-protein coupled receptor Natriuretic peptide receptor 3, implicated in paracrine signaling, was upregulated 4.70-fold. Conclusions: Although Hhex is dispensable for adult pancreatic function, ablation of Hhex in pancreatic progenitors results in profound pancreatitis that is consistent with primary ductal hypertension. Our data highlight the critical role of paracrine signaling in maintaining ductal homeostasis, especially in early life, and support ductal hypersecretion as a novel etiology of pediatric chronic pancreatitis. Overall design: Pancreatic primary ductal cells (PDCs) were isolated from uninduced adult HhexL/L;Sox9CreERT2 (n=2) and littermate control HhexL/L (n=2) mice. PDCs were treated with 500nM 4-hydroxytamoxifen in vitro for 4 days, and then RNA was collected for transcriptome analysis.
Publication Title
Spontaneous Pancreatitis Caused by Tissue-Specific Gene Ablation of <i>Hhex</i> in Mice.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 33 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
Tissue-specific differentiation and inflammatory programmes are thought to independently contribute to disease. The orphan nuclear receptor NR5A2 is a key regulator of pancreas differentiation, and SNPs in and near the human gene are associated with risk of pancreatic cancer. In mice, Nr5a2 heterozygosity sensitizes the pancreas to damage, impairs regeneration, and cooperates with mutant Kras in tumor progression. Through transcriptomic analysis, we uncovered a basal pre-inflammatory state in the pancreas of heterozygous mice that is reminiscent of pancreatitis-induced inflammation and is conserved in histologically normal human pancreata with reduced Nr5a2 mRNA expression. In mice, Nr5a2 undergoes a dramatic transcriptional switch from tissue-specific to inflammatory loci, which promotes AP-1-dependent inflammatory gene transcription. Deletion of c-Jun in the pancreas of Nr5a2+/- mice rescues the pre-inflammatory phenotype and the defective regenerative response to damage. These findings provide compelling evidence that the same transcriptional networks supporting homeostasis in normal tissue can be subverted to foster inflammation upon genetic or environmental constraints. Overall design: A mild acute pancreatitis was induced by seven hourly injections of the CCK analog caerulein (Bachem) at 50 ug/kg. Briefly, animals were weighted before the beginning of the procedure and caerulein was administered i.p. Mice were sacrificed by cervical dislocation 8h, 24h,and 48h after the first injection. Three animals of each genotype and timepoint were analysed.
Publication Title
Transcriptional regulation by NR5A2 links differentiation and inflammation in the pancreas.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Plasmodium falciparum
- 6 Downloadable Samples
- Affymetrix Plasmodium/Anopheles Genome Array (plasmodiumanopheles)
Description
P. falciparum NF54 proliferates under micro-aerophilic conditions in an environment of 3% O2, 4% CO2, 93% N2. This strain was gradually adapted to proliferate under standard tissue culture conditions of 5% CO2/95% air (~19% O2) to generate P. falciparum HOX. We compared global gene expression profiles of the two strains to identify differences, if any.
Publication Title
Model system to define pharmacokinetic requirements for antimalarial drug efficacy.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
BACKGROUND: Cadmium is implicated in prostate carcinogenesis, but its oncogenic action remains unclear.
Publication Title
Transcriptome analyses in normal prostate epithelial cells exposed to low-dose cadmium: oncogenic and immunomodulations involving the action of tumor necrosis factor.
Sample Metadata Fields
Sex
View Samples- Arabidopsis thaliana
- 4 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Piriformospora indica, an endophytic fungus of Sebacinales, colonizes the roots of many plant species including Arabidopsis thaliana. The symbiotic interaction promotes plant per-formance, growth and resistance/tolerance against abiotic and biotic stress. We demonstrate that exudated compounds from the fungus activate stress and defense responses in the Arabidopsis roots and shoots before the two partners are in physical contact. They induce stomata closure, stimulate reactive oxygen species (ROS) production, stress-related phytohormone accumulation and activate defense and stress genes in the roots and/or shoots. Once a physical contact is established, the stomata re-open, ROS and phytohormone levels decline, and the gene expression pattern indicates a shift from defense to mutualistic interaction.
Publication Title
The interaction of Arabidopsis with Piriformospora indica shifts from initial transient stress induced by fungus-released chemical mediators to a mutualistic interaction after physical contact of the two symbionts.
Sample Metadata Fields
Age, Specimen part
View Samples