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GSE21166
Homo sapiens
90 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Medulloblastoma is the most common malignant pediatric brain tumor, and mechanisms underlying its development are poorly understood. We identified recurrent amplification of the miR-17/92 polycistron proto-oncogene in 6% of pediatric medulloblastomas by high-resolution single-nucleotide polymorphism genotyping arrays and subsequent interphase fluorescence in situ hybridization on a human medulloblastoma tissue microarray. Profiling the expression of 427 mature microRNAs (miRNA) in a series of 90 primary human medulloblastomas revealed that components of the miR-17/92 polycistron are the most highly up-regulated miRNAs in medulloblastoma. Expression of miR-17/92 was highest in the subgroup of medulloblastomas associated with activation of the sonic hedgehog (Shh) signaling pathway compared with other subgroups of medulloblastoma. Medulloblastomas in which miR-17/92 was up-regulated also had elevated levels of MYC/MYCN expression. Consistent with its regulation by Shh, we observed that Shh treatment of primary cerebellar granule neuron precursors (CGNP), proposed cells of origin for the Shh-associated medulloblastomas, resulted in increased miR-17/92 expression. In CGNPs, the Shh effector N-myc, but not Gli1, induced miR-17/92 expression. Ectopic miR-17/92 expression in CGNPs synergized with exogenous Shh to increase proliferation and also enabled them to proliferate in the absence of Shh. We conclude that miR-17/92 is a positive effector of Shh-mediated proliferation and that aberrant expression/amplification of this miR confers a growth advantage to medulloblastomas.
Publication Title
The miR-17/92 polycistron is up-regulated in sonic hedgehog-driven medulloblastomas and induced by N-myc in sonic hedgehog-treated cerebellar neural precursors.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 3 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Dendritic cells (DCs) in tissues and lymphoid organs comprise distinct functional subsets that differentiate in situ from circulating progenitors. Tissue-specific signals that regulate DC subset differentiation are poorly understood. We report that DC-specific deletion of the Notch2 receptor caused a reduction of DC populations in the spleen. Within the splenic CD11b+ DCs, Notch signaling blockade ablated a distinct population marked by high expression of adhesion molecule Esam. The Notch-dependent Esamhi DC subset also required lymphotoxin beta receptor signaling, proliferated in situ and facilitated efficient CD4+ T cell priming. The Notch-independent Esamlo DCs expressed monocyte-related genes and showed superior cytokine responses. In addition, Notch2 deletion led to the loss of CD11b+ CD103+ DCs in the intestinal lamina propria and to the corresponding decrease of IL-17-producing CD4+ T cells in the intestine. Thus,Notch2 is a common differentiation signal for T cell-priming CD11b+ DC subsets in the spleen and intestine.
Publication Title
Notch2 receptor signaling controls functional differentiation of dendritic cells in the spleen and intestine.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 58 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To identify molecular subtypes of medulloblastoma we have profiled a series of 62 medulloblastoma tumors. Unsupervised hierarchical cluster analysis of these data identified 5 distinct molecular subtypes.
Publication Title
Integrated genomics identifies five medulloblastoma subtypes with distinct genetic profiles, pathway signatures and clinicopathological features.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 35 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
Purpose: Myxopapillary ependymoma (MPE) is a distinct histological variant of ependymoma arising commonly in the spinal cord. Despite an overall favorable prognosis, distant metastases, subarachnoid dissemination, and late recurrences have been reported. Currently the only effective treatment for MPE is gross-total resection. We characterized the genomic and transcriptional landscape of spinal ependymomas in an effort to delineate the genetic basis of this disease and identify new leads for therapy.
Publication Title
Spinal Myxopapillary Ependymomas Demonstrate a Warburg Phenotype.
Sample Metadata Fields
Sex, Specimen part, Disease stage
View Samples- Homo sapiens
- 101 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Gene expression (mRNA) profiling of human ependymomas
Publication Title
Delineation of two clinically and molecularly distinct subgroups of posterior fossa ependymoma.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Quiescent and dividing hemopoietic stem cells (HSC) display marked differences in their ability to move between the peripheral circulation and the bone marrow. Specifically, long-term engraftment potential predominantly resides in the quiescent HSC subfraction, and G-CSF mobilization results in the preferential accumulation of quiescent HSC in the periphery. In contrast, stem cells from chronic myeloid leukemia (CML) patients display a constitutive presence in the circulation. To understand the molecular basis for this, we have used microarray technology to analyze the transcriptional differences between dividing and quiescent, normal, and CML-derived CD34+ cells.
Publication Title
Transcriptional analysis of quiescent and proliferating CD34+ human hemopoietic cells from normal and chronic myeloid leukemia sources.
Sample Metadata Fields
Specimen part, Disease, Subject
View Samples- Mus musculus
- 56 Downloadable Samples
Illumina HiSeq 2500
Description
Plasmacytoid dendritic cells (pDCs) are an immune subset devoted to the production of high amounts of type 1 interferons in response to viral infections. While conventional dendritic cells (cDCs) originate mostly from a common dendritic cell progenitor (CDP), pDCs have been shown to develop from both CDPs and common lymphoid progenitors (CLP). Here we found that pDCs developed predominantly from IL7R+ lymphoid progenitor cells. Expression of SiglecH and Ly6D defined pDC lineage commitment along the lymphoid branch. Transcriptional characterization of SiglecH+Ly6D+ precursors indicated that pDC development requires high expression of the transcription factor IRF8, while pDC identity relies on TCF4. RNA sequencing of IL7R+ lymphoid and CDP-derived pDCs mirrored the heterogeneity of mature pDCs observed by single-cell analysis. Both mature pDC subsets are able to secrete type 1 interferons, but only myeloid-derived pDCs share with cDCs their ability to process and present antigen. Overall design: Bulk RNA Seq was performed from sort purified DN, SP and DP lymphoid progenitors and BM pDCs of 4 individual mice
Publication Title
Distinct progenitor lineages contribute to the heterogeneity of plasmacytoid dendritic cells.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- NextSeq 500
Description
Plasmacytoid dendritic cells (pDCs) are an immune subset devoted to the production of high amounts of type 1 interferons in response to viral infections. While conventional dendritic cells (cDCs) originate mostly from a common dendritic cell progenitor (CDP), pDCs have been shown to develop from both CDPs and common lymphoid progenitors (CLP). Here we found that pDCs developed predominantly from IL7R+ lymphoid progenitor cells. Expression of SiglecH and Ly6D defined pDC lineage commitment along the lymphoid branch. Transcriptional characterization of SiglecH+Ly6D+ precursors indicated that pDC development requires high expression of the transcription factor IRF8, while pDC identity relies on TCF4. RNA sequencing of IL7R+ lymphoid and CDP-derived pDCs mirrored the heterogeneity of mature pDCs observed by single-cell analysis. Both mature pDC subsets are able to secrete type 1 interferons, but only myeloid-derived pDCs share with cDCs their ability to process and present antigen. Overall design: BM and splenic pDCs were sorted from 3 mice and 3000 cells/sample were used for single cell RNA Seq (10x genomics)
Publication Title
Distinct progenitor lineages contribute to the heterogeneity of plasmacytoid dendritic cells.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 763 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
Affimetrix Human Gene 1.1 ST Array profiling of 763 primary medullobalstoma samples used for identification of Medullobastoma subtypes
Publication Title
Intertumoral Heterogeneity within Medulloblastoma Subgroups.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Variable strengths of T cell receptor (TCR) signaling can produce divergent outcomes for T cell development and function. The mechanisms leading to different outcomes are incompletely understood, but may include distinct activation thresholds for different transcription factors as well as distinct sensitivities among target genes to transcription factors. IRF4 is one transcription factor implicated in responses to variable TCR signal strength. IRF4 expression increases uniformly with increasing TCR signal strength (i.e., analog), but it is unclear how IRF4 induced distinct genes at different levels, rather than different amounts of the same genes. Here, we analyzed global gene expression in TH2 cells and used ChIP-seq to define the relationship between TCR signal strength, enhancer occupancy and transcriptional activity for BATF/IRF4-dependent genes. We show that enhancers exhibit a spectrum of affinity for the BATF/IRF4 ternary complex mediate graded responsiveness of individual genes to increasing TCR signal strength. Differential gene induction by BATF and IRF4 occurs through interaction with enhancer elements of different affinity for BATF/IRF4 complexes. The increased resolution of factor binding site identified using ChIP-exo allowed the identification of a novel AICE2 motif binding BATF/IRF4 with higher affinity and that this may explain the protective role of a single nucleotide polymorphism in the CTLA-4 locus known to decrease the incidence of autoimmune diseases.
Publication Title
Quality of TCR signaling determined by differential affinities of enhancers for the composite BATF-IRF4 transcription factor complex.
Sample Metadata Fields
Specimen part
View Samples