Gangliogliomas, the most frequent neoplasms in patients with pharmacoresistant focal epilepsies, are characterized by histological combinations of glial and dysplastic neuronal elements, a highly differentiated phenotype and rare gene mutations.<br></br><br></br>Here, we have used discrete microdissected ganglioglioma and adjacent control brain tissue obtained from the neurosurgical access to the tumour of identical patients (n = 6) carefully matched for equivalent glial and neuronal elements in an amount sufficient for oligonucleotide microarray hybridization without repetitive amplification. Multivariate statistical analysis identified a rich profile of genes with altered expression in gangliogliomas.
Array analysis of epilepsy-associated gangliogliomas reveals expression patterns related to aberrant development of neuronal precursors.
Sex, Specimen part, Disease, Subject
View SamplesViral infections of the CNS are of increasing concern, especially among immunocompromised populations. Rodent models are often inappropriate for studies of CNS infection, as many viruses, including JC Virus (JCV) and HIV, cannot replicate in rodent cells. Consequently, human fetal brain-derived multipotential CNS progenitor cells (NPCs) that can be differentiated into neurons, oligodendrocytes, or astrocytes, have served as a model for CNS studies. NPCs can be non-productively infected by JCV, while infection of progenitor-derived astrocytes (PDAs) is robust. We profiled cellular gene expression at multiple times during differentiation of NPCs to PDAs. Several activated transcription factors show commonality between cells of the brain in which JCV replicates and lymphocytes in which JCV is likely latent. Bioinformatic analysis determined transcription factors that may influence the favorable transcriptional environment for JCV in PDAs. This study attempts to provide a framework for understanding the functional transcriptional profile necessary for productive JCV infection.
Differentiation of human fetal multipotential neural progenitor cells to astrocytes reveals susceptibility factors for JC virus.
Specimen part, Time
View SamplesHuman diffuse intrinsic pontine gliomas (DIPG) are an aggressive form of pediatric brain tumors that arise in the pons in young children thus resulting in significant morbidity and very poor survival. Recent data suggest that mutations in the histone H3.3 variant are often found in these tumors, though the mechanism of their contribution to oncogenesis remains to be elucidated. Here we report that the combination of constitutive PDGFRA activation and p53 suppression as well as expression of the K27M mutant form of the histone H3.3 variant leads to neoplastic transformation of hPSC-derived neural precursors. Our study demonstrates that human ES cells represent an excellent platform for the modeling of human tumors in vitro and in vivo, which could potentially lead to the elucidation of the molecular mechanisms underlying neoplastic transformation and the identification of novel therapeutic targets.
Use of human embryonic stem cells to model pediatric gliomas with H3.3K27M histone mutation.
Specimen part
View SamplesCD4+ T cells from 8-12 week female mice were isolated from wt and AhR-/- mice 24h after injection of 10g/kg TCDD or solvent control.
Transcriptional signatures of immune cells in aryl hydrocarbon receptor (AHR)-proficient and AHR-deficient mice.
Sex, Treatment
View SamplesEffect of an immunosupressive dose of TCDD, a ligand for the aryl hydrocarbon receptor, on the gene expression profile of fetal DN thymocytes and thymic emigrants
Transcriptional signatures of immune cells in aryl hydrocarbon receptor (AHR)-proficient and AHR-deficient mice.
Specimen part, Treatment
View Samples8-12 week, female C57BL/6 mice were injected with 10 g/kg TCDD or solvent control. CD8+ T cells from spleen were FACS purified and submitted to transcription profiling
Transcriptional signatures of immune cells in aryl hydrocarbon receptor (AHR)-proficient and AHR-deficient mice.
Sex, Treatment
View SamplesEffect of the over activation of the aryl hydrocarbon receptor on gene expression of spleen derived dendritic cells.
Transcriptional signatures of immune cells in aryl hydrocarbon receptor (AHR)-proficient and AHR-deficient mice.
Sex, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Expression profiling and functional analysis of Populus WRKY23 reveals a regulatory role in defense.
Specimen part
View SamplesTo investigate the function of poplar WRKY23, we generated PtWRKY23-overexpressing and -underexpressing (RNAi) plants. Transgenic plants were inoculated with Melampsora rust or mock-inoculated for assessment of rust-resistance and for gene expression profiling using the poplar Affymetrix GeneChip to study the consequences of PtWRKY23 overexpression and underexpression. Transcriptome analysis of PtWRKY23 overexpressors revealed a significant overlap with the Melampsora-infection response. Transcriptome analysis also indicated that PtWRKY23 affects redox homeostasis and cell wall-related metabolism.
Expression profiling and functional analysis of Populus WRKY23 reveals a regulatory role in defense.
Specimen part
View SamplesIt is currently unknown how extensively the double-stranded RNA binding protein Staufen (Stau)1 is utilized by mammalian cells to regulate gene expression. To date, Stau1 binding to the 3 untranslated region (3UTR) of ARF1 mRNA has been shown to target ARF1 mRNA for Stau1-mediated mRNA decay (SMD). ARF1 SMD depends on translation and recruitment of the nonsense-mediated mRNA decay factor Upf1 to the ARF1 3UTR by Stau1. Here, we use microarray analyses to examine changes in the abundance of cellular mRNAs that occur when Stau1 is depleted. Results indicate that 1.1% and 1.0% of the 11,569 HeLa-cell transcripts that were analyzed are, respectively, upregulated and downregulated at least two-fold in three independently performed experiments. Additionally, we localize the Stau1 binding site to the 3UTR of four mRNAs that we define as natural SMD targets. Together, these and substantiating results suggest that Stau1 influences the expression of a wide variety of physiologic transcripts and metabolic pathways.
Staufen1 regulates diverse classes of mammalian transcripts.
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