This SuperSeries is composed of the SubSeries listed below.
Cell competition is a tumour suppressor mechanism in the thymus.
Specimen part
View SamplesPilocytic astrocytomas (PA) are the most common brain tumor in pediatric patients and can cause significant morbidity, including chronic neurological deficiencies. They are characterized by activating alterations in the mitogen-activated protein kinase (MAPK) pathway, but little else is known about their development. To further define their molecular development, we analysed the global DNA methylation profiles of 61 PAs and 6 normal cerebellum samples and integrated this data with transcriptome profiling. These data revealed two subgroups of PA that separate according to tumor location (infratentorial versus supratentorial), and identified key neural developmental genes that are differentially methylated between the two groups. Significant expression differences were identified for the majority of differentially methylated genes, and these were unexpectedly associated with a strong positive correlation between methylation and expression. We also identified a large number of differentially methylated/expressed genes between cerebellar PAs and normal cerebellum, which included additional developmental genes.
Differential expression and methylation of brain developmental genes define location-specific subsets of pilocytic astrocytoma.
Sex, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
BCAT1 restricts αKG levels in AML stem cells leading to IDHmut-like DNA hypermethylation.
Cell line, Treatment
View SamplesAblation of the Creb1 gene in forebrain neurons was performed using the Cre/loxP system, with the recombinase expressed from the Camk2alfa promoter. Mice were crossed into the Crem KO background to prevent compensation of CREB loss by CREM overexpression.
CREB has a context-dependent role in activity-regulated transcription and maintains neuronal cholesterol homeostasis.
No sample metadata fields
View SamplesAnalysis of differences in gene expression between different cell types of the vascular niche. Looking for candidates, that could potentially be up-or downregualted in the different cell types
Pericyte-expressed Tie2 controls angiogenesis and vessel maturation.
Specimen part
View SamplesGlioblastoma (GBM) is an incurable brain tumor carrying a dismal prognosis, which displays considerable heterogeneity. We have recently identified recurrent H3F3A mutations affecting two critical positions of histone H3.3 (K27, G34) in one-third of pediatric GBM. Here we show that each of these H3F3A mutations defines an epigenetic subgroup of GBM with a distinct global methylation pattern, and are mutually exclusive with IDH1 mutation (characterizing a CpG-Island Methylator Phenotype (CIMP) subgroup). Three further epigenetic subgroups were enriched for hallmark genetic events of adult GBM (EGFR amplification, CDKN2A/B deletion) and/or known transcriptomic signatures. We also demonstrate that the two H3F3A mutations give rise to GBMs in separate anatomic compartments, with differential regulation of OLIG1/2 and FOXG1, possibly reflecting different cellular origins.
Hotspot mutations in H3F3A and IDH1 define distinct epigenetic and biological subgroups of glioblastoma.
Sex
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Krüppel-like factor 4 (KLF4) inactivation in chronic lymphocytic leukemia correlates with promoter DNA-methylation and can be reversed by inhibition of NOTCH signaling.
Sex
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Translational regulation of specific mRNAs controls feedback inhibition and survival during macrophage activation.
Specimen part, Time
View SamplesWhen macrophages encounter pathogens, they transiently induce an orchestrated cascade of pro- and anti-inflammatory genes. We systematically analyzed the contribution of translational regulation to the early phase of macrophage activation. While the expression of most cytokines is regulated by changes in mRNA levels, de-repression of translation was found to permit expression of many feedback inhibitors of the inflammatory response. This includes NF-kB inhibitors (IkBd, IkBz, Nr4a1, Ier3), a p38 MAPK antagonist (Dusp1) and post-transcriptional suppressors of cytokine expression (TTP and Zc3h12a). Ier3 is tightly co-regulated with TNF at the level of mRNA abundance and translation. Macrophages lacking Ier3 show reduced survival upon activation, indicating that induction of Ier3 is required to protect macrophages from lipopolysaccharide-induced cell death. Our analysis reveals an important role of translational regulation in the resolution of inflammation and macrophage survival.
Translational regulation of specific mRNAs controls feedback inhibition and survival during macrophage activation.
Specimen part
View SamplesExpression analyses comparing c-Fos expressing keratinocytes vs non-expressing controls.
Inflammation-mediated skin tumorigenesis induced by epidermal c-Fos.
Specimen part, Treatment, Time
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