Thymic iNKT cell development is divided into four stages (stage 0-3) that are characterised, in C57BL/6 mouse strain, by the differential expression of surface markers, such as CD24, CD44 and NK1.1. During transition from immature to mature iNKT cell subsets, gene expression is tightly regulated. Here, we used microarray analysis to detail the influence of the transcriptional regulator ID3 during iNKT cell maturation in the thymus.
Essential functions for ID proteins at multiple checkpoints in invariant NKT cell development.
Age, Specimen part
View SamplesE47 is a basic Helix Loop Helix (bHLH) transcription factor that has important roles in cell fate determination and differentiation of many cell types. In the nervous system E47 heterodimerizes with tissue-specific, pro-neural bHLH transcription factors and activates downstream target genes. To identify the relevant target genes of bHLH transcription factors in neural cells, we performed gene expression profiling of the human neuroblastoma cell line SK-N-SH engineered to acutely express ectopic E47 by an adenoviral vector. The experiments were done at two time points following adenoviral infection, 8 hours and 20 hours. Genes induced by E47 after 8 hours are likely to be direct targets of this transcription factor.
Degradation of Id2 by the anaphase-promoting complex couples cell cycle exit and axonal growth.
Specimen part, Cell line, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The transcriptional network for mesenchymal transformation of brain tumours.
Time
View SamplesUsing a novel combination of cellular-network reverse-engineering algorithms and experimental validation assays, we identified a transcriptional module, including six transcription factors that synergistically regulates the mesenchymal signature of malignant glioma. This is a poorly understood molecular phenotype, never observed in normal neural tissue. It represents the hallmark of tumor aggressiveness in high-grade glioma, and its upstream regulation is so far unknown. Overall, the newly discovered transcriptional module regulates >74% of the signature genes, while two of its transcription factors (C/EBP and Stat3) display features of initiators and master regulators of mesenchymal transformation. Ectopic co-expression of C/EBP and Stat3 is sufficient to reprogram neural stem cells along the aberrant mesenchymal lineage, while simultaneously suppressing differentiation along the default neural lineages (neuronal and glial). Conversely, silencing the two transcription factors in human glioma cell lines and glioblastoma-derived tumor initiating cells leads to collapse of the mesenchymal signature with corresponding loss of tumor aggressiveness in vitro and in immunodeficient mice after intracranial injection. In human tumor samples, combined expression of C/EBP and Stat3 correlates with mesenchymal differentiation of primary glioma and is a predictor of poor clinical outcome. Taken together, these results reveal that activation of a small regulatory module inferred from the accurate reconstruction of transcriptional networks is necessary and sufficient to initiate and maintain an aberrant phenotypic state in eukaryotic cells.
The transcriptional network for mesenchymal transformation of brain tumours.
Time
View SamplesUsing a novel combination of cellular-network reverse-engineering algorithms and experimental validation assays, we identified a transcriptional module, including six transcription factors that synergistically regulates the mesenchymal signature of malignant glioma. This is a poorly understood molecular phenotype, never observed in normal neural tissue. It represents the hallmark of tumor aggressiveness in high-grade glioma, and its upstream regulation is so far unknown. Overall, the newly discovered transcriptional module regulates >74% of the signature genes, while two of its transcription factors (C/EBP and Stat3) display features of initiators and master regulators of mesenchymal transformation. Ectopic co-expression of C/EBP and Stat3 is sufficient to reprogram neural stem cells along the aberrant mesenchymal lineage, while simultaneously suppressing differentiation along the default neural lineages (neuronal and glial). Conversely, silencing the two transcription factors in human glioma cell lines and glioblastoma-derived tumor initiating cells leads to collapse of the mesenchymal signature with corresponding loss of tumor aggressiveness in vitro and in immunodeficient mice after intracranial injection. In human tumor samples, combined expression of C/EBP and Stat3 correlates with mesenchymal differentiation of primary glioma and is a predictor of poor clinical outcome. Taken together, these results reveal that activation of a small regulatory module, inferred from the accurate reconstruction of transcriptional networks, is necessary and sufficient to initiate and maintain an aberrant phenotypic state in eukaryotic cells.
The transcriptional network for mesenchymal transformation of brain tumours.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Epigenetic Regulation of ZBTB18 Promotes Glioblastoma Progression.
Cell line
View SamplesThe transcriptional repressor ZBTB18 was overexpressed in the brain tumor xenoline JX6 by lentiviral transduction. Three independent transduction were performed (biological replicates) and analyzed by gene expression aray. Gene set enrichemnt analysis (GSEA) showed changes in the expression of mesenchymal signature. A subset of genes was further valiadted by qPCR. These results indicate a role of ZBTB18 as repressor of mesenchymal genes in Glioblastoma.
Epigenetic Regulation of ZBTB18 Promotes Glioblastoma Progression.
Cell line
View SamplesThe transcriptional repressor ZBTB18 was overexpressed in the brain tumor stem cell-like BTSC233 by lentiviral transduction. Three independent transduction were performed (biological replicates) and analyzed by gene expression aray. Gene set enrichemnt analysis (GSEA) showed changes in the expression of mesenchymal signature. A subset of genes was further valiadted by qPCR. These results indicate a role of ZBTB18 as repressor of mesenchymal genes in Glioblastoma.
Epigenetic Regulation of ZBTB18 Promotes Glioblastoma Progression.
Cell line
View SamplesTo identify the role of the SH3PXD2A-HTRA1 fusion on gene expression in Schwann cells
The genomic landscape of schwannoma.
Specimen part
View SamplesThis dataset contains gene expression data from the NRC series (Neuroblastoma Research Consortium) for a total of 283 primary neuroblastoma tumors. All tumor samples are fully annotated including patient age at diagnosis, overall and progresison free survival and MYCN amplification status, enabling subgroup analysis, survival analysis and gene expression network analysis.
Cross-Cohort Analysis Identifies a TEAD4-MYCN Positive Feedback Loop as the Core Regulatory Element of High-Risk Neuroblastoma.
No sample metadata fields
View Samples