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GSE37516
Mus musculus
9 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The culture of neural stem cells (NSCs) as floating neurospheres has become widely used as an experimental model to analyse the properties of NSCs. Although the neurosphere model has existed for two decades, there is still no standard protocol to grow NSCs in this way. Thus, we have analysed the consequences of the frequency of growth factor (FGF-2 and EGF) addition to embryonic and adult olfactory bulb stem cells (eOBSCs and aOBSCs) cultures, specifically in terms of proliferation, cell cycle progression, death and differentiation, as well as on global changes in gene expression and signaling pathways. We found that addition of FGF-2 and EGF every two or four days rather than daily significantly reduces the volume of the neurospheres and the total number of cells, changes that were more evident in aOBSC than in eOBSC cultures. The reduction in neurosphere size was mainly due to an increase in cell death and occurs without major changes in the cell cycle parameters tested. Moreover, partial deprivation of FGF-2 and EGF produces a mild increase in aOBSC differentiation during the proliferative phase. Remarkably, these effects were accompanied by a significant upregulation in the expression of genes involved in cell death regulation (Cryab), lipid catabolic processes (Pla2g7), cell adhesion (Dscaml1), cell differentiation (Dscaml1, Gpr17, S100b) and signal transduction (Gpr17, Ndrg2), among others. These findings support that continuous supply of FGF-2 and EGF is critical to maintain the viability/survival of NSCs in culture and reveals novel molecular hallmarks of NSC maintenance/survival and expansion in response to these growth factors.
Publication Title
A global transcriptome analysis reveals molecular hallmarks of neural stem cell death, survival, and differentiation in response to partial FGF-2 and EGF deprivation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus, Homo sapiens, Rattus norvegicus
- 1938 Downloadable Samples
- Affymetrix Rat Gene 2.0 ST Array (ragene20st), Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2), Affymetrix Rat Expression 230A Array (rae230a), Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm), Affymetrix Rat Genome 230 2.0 Array (rat2302), Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Phenobarbital mediates an epigenetic switch at the constitutive androstane receptor (CAR) target gene Cyp2b10 in the liver of B6C3F1 mice.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment, Subject, Time
View Samples- Rattus norvegicus
- 119 Downloadable Samples
Affymetrix Rat Gene 2.0 ST Array (ragene20st), Affymetrix Rat Expression 230A Array (rae230a)
Description
The carcinogenic potential of chemicals is currently evaluated with rodent life-time bioassays, which are time consuming, and expensive with respect to cost, number of animals and amount of compound required. For insight into early mechanisms of non-genotoxoc carcinogenesis and for identification of potential early biomarkers of non-genotoxic carcinogenesis, groups of rats were treated with a range of known non-genotoxic carcinogens for a period of 14, 28, or 90 days, and liver tissue was harvested for expression profiling. Control groups were treated with appropriate vehicles.
Publication Title
Phenobarbital mediates an epigenetic switch at the constitutive androstane receptor (CAR) target gene Cyp2b10 in the liver of B6C3F1 mice.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 40 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Phenobarbital mediates an epigenetic switch at the constitutive androstane receptor (CAR) target gene Cyp2b10 in the liver of B6C3F1 mice.
Sample Metadata Fields
Sex, Specimen part, Treatment, Subject
View Samples- Rattus norvegicus
- 60 Downloadable Samples
- Affymetrix Rat Expression 230A Array (rae230a), Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Conventional notion regards the action of non-genotoxic carcinogens (NGC) an autonomous process largely confined to parenchymal cells. Here we aim to elucidate the role of the hepatic mesenchyme for the action of two prototypical NGC, phenobarbital (PB), an anti-epileptic drug, and cyproterone acetate (CPA) a gestagen used in contraceptive pills.
Publication Title
Phenobarbital mediates an epigenetic switch at the constitutive androstane receptor (CAR) target gene Cyp2b10 in the liver of B6C3F1 mice.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Rattus norvegicus
- 47 Downloadable Samples
- Affymetrix Rat Expression 230A Array (rae230a), Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Here we investigate the difference in global gene expression in different tumor types found in the liver of rats after NNM-initiation/PB-promotion of tumor growth. We aim to identify tumor characteristic expression in nodules, focii, adenomas and carcinomas.
Publication Title
Phenobarbital mediates an epigenetic switch at the constitutive androstane receptor (CAR) target gene Cyp2b10 in the liver of B6C3F1 mice.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 40 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Evidence suggests that epigenetic perturbations are involved in the adverse effects associated with some drugs and toxicants, including certain classes of non-genotoxic carcinogens. Such epigenetic changes (altered DNA methylation and covalent histone modifications) may take place at the earliest stages of carcinogenesis and their identification holds great promise for biomedical research. Here, we evaluate the sensitivity and specificity of genome-wide epigenomic and transcriptomic profiling in phenobarbital (PB)-treated B6C3F1 mice, a well-characterized rodent model of non-genotoxic liver carcinogenesis. Methylated DNA Immunoprecipitation (MeDIP)-coupled microarray profiling of 17,967 promoter regions and 4,566 intergenic CpG islands was combined with genome-wide mRNA expression profiling to identify liver tissue-specific PB-mediated DNA methylation and transcriptional alterations. Only a limited number of significant anti-correlations were observed between PB-induced transcriptional and promoter-based DNA methylation perturbations. However, the constitutive androstane receptor (CAR) target gene Cyp2b10 was found to be concomitantly hypomethylated and transcriptionally activated in a liver tissue-specific manner following PB treatment. Furthermore, analysis of active and repressive histone modifications using chromatin immunoprecipitation revealed a strong PB-mediated epigenetic switch at the Cyp2b10 promoter. Our data reveal that PB-induced transcriptional perturbations are not generally associated with broad changes in the DNA methylation status at proximal promoters and suggest that the drug-inducible CAR pathway regulates an epigenetic switch from repressive to active chromatin at the target gene Cyp2b10. This study demonstrates the utility of integrated epigenomic and transcriptomic profiling for elucidating early mechanisms and biomarkers of non-genotoxic carcinogenesis.
Publication Title
Phenobarbital mediates an epigenetic switch at the constitutive androstane receptor (CAR) target gene Cyp2b10 in the liver of B6C3F1 mice.
Sample Metadata Fields
Sex, Specimen part, Treatment, Subject
View Samples- Mus musculus
- 23 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Signaling through the Wnt/b-catenin pathway is a crucial determinant of hepatic zonal gene expression, liver development, regeneration, and tumorigenesis. The gene encoding b-catenin is called Ctnnb1. We have previously shown, that liver tumour promotion mediated by the model tumour promoter phenobarbital (PB) is completely lost in mice, where Ctnnb1 has been conditionally knocked out in hepatocytes (CTNNB1KO mice; Rignall et al., Carcinogenesis 32, 52-57, 2010). In the present study, the effect of a 12 weeks PB exposure on the liver miRNA expression pattern was investigated, in order to potentially get information on the nature of the loss of promotional activity in the CTNNB1KO mice.
Publication Title
Phenobarbital mediates an epigenetic switch at the constitutive androstane receptor (CAR) target gene Cyp2b10 in the liver of B6C3F1 mice.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Conventional notion regards the action of non-genotoxic carcinogens (NGC) an autonomous process largely confined to parenchymal cells. Here we aim to elucidate the role of the hepatic mesenchyme for the action of a prototypical NGC, phenobarbital (PB), an anti-epileptic drug.
Publication Title
Phenobarbital mediates an epigenetic switch at the constitutive androstane receptor (CAR) target gene Cyp2b10 in the liver of B6C3F1 mice.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
3 eosinophilic esophagitis biopsies, cultured and stimulated with IL-13 : each of them was either left unstimulated or stimulated (100ng for 48h)
Publication Title
IL-13 involvement in eosinophilic esophagitis: transcriptome analysis and reversibility with glucocorticoids.
Sample Metadata Fields
No sample metadata fields
View Samples