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GSE129309
Mus musculus
6 Downloadable Samples
Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Group-2 innate lymphoid cells (ILC2) serve crucial function in allergy and asthma. Activated ILC2 rapidly proliferate and secret large amounts of type-2 cytokines, such as IL-5 and IL-13. Mechanisms underlying still remain ambiguous. Here we report that Myc is required for ILC2 proliferation and activation in allergic airway inflammation. Inhibition of Myc impair the ILC2 proliferation in vivo and prevented ILC2-mediated airway hyperresponsiveness in vivo.
Publication Title
A critical role for c-Myc in group 2 innate lymphoid cell activation.
Sample Metadata Fields
Genotype, Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
Description
Extensive molecular profiling of leukemias and preleukemic diseases has revealed that distinct clinical entities, like acute myeloid (AML) and T-lymphoblastic leukemia, share the same pathogenetic mutations. It is not well understood how the cell of origin, accompanying mutations, extracellular signals or structural differences in a mutated gene determine the phenotypic identity of the malignant disease. We studied the relationship of different protein domains of the MN1 oncogene and their effect on the leukemic phenotype, building on the ability of MN1 to induce leukemia without accompanying mutations. We found that the most C-terminal domain of MN1 was required to block myeloid differentiation at an early stage, and deletion of an extended C-terminal domain resulted in loss of myeloid identity and cell differentiation along the T-cell lineage in vivo. Megakaryocytic/erythroid lineage differentiation was blocked by the most N-terminal domain. In addition, the N-terminus was required for proliferation and leukemogenesis in vitro and in vivo through upregulation of HoxA9, HoxA10 and Meis2. Our results provide evidence that a single oncogene can modulate cellular identity of leukemic cells based on its active domains. It is therefore likely that different mutations in the same oncogene may impact cell fate decisions and phenotypic appearance of malignant diseases.
Publication Title
Cell fate decisions in malignant hematopoiesis: leukemia phenotype is determined by distinct functional domains of the MN1 oncogene.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus, Rattus norvegicus, Homo sapiens
- 56 Downloadable Samples
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- Mus musculus
- 40 Downloadable Samples
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- Mus musculus
- 40 Downloadable Samples
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