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 SamplesInhibitor of apoptosis (IAP) proteins constitute a conserved family of molecules which regulate both apoptosis and receptor signaling. They are often deregulated in cancer cells and represent potential targets for therapy. In our work, we investigated the effect of IAP inhibition in vivo to identify novel downstream genes expressed in an IAP-dependent manner that could contribute to cancer aggressiveness. To this end, immunocompromised mice engrafted subcutaneously with the triple negative breast cancer MDA-MB231 cell line were treated with SM83, a pan-IAP inhibitor developed by us, and tumor nodules were profiled for gene expression. Our work suggests that IAP-targeted therapy could contribute to EGFR inhibition and the reduction of its downstream mediators. This approach could be particularly effective in cells characterized by high levels of EGFR and Snai2, such as triple negative breast cancer.
cIAP1 regulates the EGFR/Snai2 axis in triple-negative breast cancer cells.
Specimen part, Treatment
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
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