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GSE44971
Homo sapiens
58 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Pilocytic 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.
Publication Title
Differential expression and methylation of brain developmental genes define location-specific subsets of pilocytic astrocytoma.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Striatal medium spiny neurons (MSN) are critically involved in motor control, and their degeneration is a principal component of Huntingtons disease. We find that the transcription factor Ctip2 (also known as Bcl11b) is central to MSN differentiation and striatal development. Within the striatum, it is expressed by all MSN, while it is excluded from essentially all striatal interneurons. In the absence of Ctip2, MSN do not fully differentiate, as demonstrated by dramatically reduced expression of a large number of MSN markers, including DARPP-32, FOXP1, Chrm4, Reelin, MOR1, GluR1, and Plexin-D1. Furthermore, MSN fail to aggregate into patches, resulting in severely disrupted patch-matrix organization within the striatum. Finally, heterotopic cellular aggregates invade the Ctip2-/- striatum suggesting a failure by MSN to repel these cells in the absence of Ctip2. In order to investigate the molecular mechanisms that underlie Ctip2-dependent differentiation of MSN and that underlie the patch-matrix disorganization in the mutant striatum, we directly compared gene expression between wild type and mutant striatum at P0. Because CTIP2-expressing MSN constitute 90-95% of the neurons within the striatum, we reasoned that we should be able to detect changes in medium spiny neuron gene expression in Ctip2 null mutants. We microdissected out small regions of striatum at matched locations in wild type and Ctip2-/- mutant littermates at P0 and investigated gene expression with Affymetrix microarrays. We selected the 153 most significant genes and further analyzed them to identify a smaller set of genes of potentially high biological relevance. In order to verify the microarray data and define the distribution of the identified genes in the striatum, we performed in situ hybridization or immunohistochemistry for 12 selected genes: Plexin-D1, Ngef, Nectin-3, Kcnip2, Pcp4L1, Neto1, Basonuclin 2, Fidgetin, Semaphorin 3e, Secretagogin, Unc5d, and Neurotensin. We find that all these genes are either specifically downregulated (Plexin-D1, Ngef, Nectin-3 Kcnip2, Pcp4L1, Neto1), or upregulated (Basonuclin 2, Fidgetin, Semaphorin 3e, Secretagogin, Unc5d, Neurotensin), in the Ctip2-/- striatum, confirming and extending the microarray results. Together, these data indicate that Ctip2 is a critical regulator of MSN differentiation, striatal patch development, and the establishment of the cellular architecture of the striatum.
Publication Title
Ctip2 controls the differentiation of medium spiny neurons and the establishment of the cellular architecture of the striatum.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 40 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Molecular characterization of choroid plexus tumors reveals novel clinically relevant subgroups.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 40 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Gene expression was assessed in a cohort of 40 choroid plexus tumors isolated from fresh-frozen tissue. We investigated unique expression patterns among tumor subgroups and refined the classification of choroid plexus tumors according to gene expression intensities.
Publication Title
Molecular characterization of choroid plexus tumors reveals novel clinically relevant subgroups.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 18 Downloadable Samples
Illumina HiSeq 2500
Description
The goal of this study is to understand the alterations in transcriptome induced by histone H3K36M mutations Overall design: Transcritome profiling of 3 cell lines cultured in vitro and 6 murine tumors
Publication Title
Histone H3K36 mutations promote sarcomagenesis through altered histone methylation landscape.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Mutations in the histone 3 variant H3.3 have been identified in one-third of pediatric glioblastomas (GBMs), but not in adult tumors. Here we show that H3.3 is a dynamic determinant of functional properties in adult GBM. H3.3 is repressed by mixed lineage leukemia 5 (MLL5) in self-renewing GBM cells. MLL5 is a global epigenetic repressor that orchestrates reorganization of chromatin structure by punctuating chromosomes with foci of compacted chromatin, favoring tumorigenic and self-renewing properties. Conversely, H3.3 antagonizes self-renewal and promotes differentiation. We exploited these epigenetic states to rationally identify two small molecules that effectively curb cancer stem cell properties in a preclinical model. Our work uncovers a role for MLL5 and H3.3 in maintaining self-renewal hierarchies in adult GBM.
Publication Title
MLL5 Orchestrates a Cancer Self-Renewal State by Repressing the Histone Variant H3.3 and Globally Reorganizing Chromatin.
Sample Metadata Fields
Specimen part, Time
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- Mus musculus
- 204 Downloadable Samples
- Illumina HiSeq 2000
Description
Cortical GABAergic interneurons constitute a highly diverse population of inhibitory neurons that are key regulators of cortical microcircuit function. An important and heterogeneous group of cortical interneurons specifically expresses the serotonin receptor 3A (5-HT3AR) but how this diversity emerges during development is poorly understood. Here we use single-cell transcriptomics to identify gene expression patterns operating in Htr3a-GFP+ interneurons during early steps of cortical circuit assembly. We identify 3 main molecular types of Htr3a-GFP+ interneurons, each displaying distinct developmental dynamics of gene expression. The transcription factor Meis2 is specifically enriched in a type of Htr3a-GFP+ interneurons spatially confined to the cortical white matter. These MEIS2 expressing interneurons appear to originate from a restricted region located at the embryonic pallial-subpallial boundary. Overall, this study identifies MEIS2 as a subclass-specific marker for 5-HT3AR-containing interstitial interneurons and demonstrates that the transcriptional and anatomical parcellation of cortical interneurons is developmentally coupled. Overall design: Single cell transcriptomics of cortical interneurons FACS sorted according to GFP-Htr3a+. Acquired from mouse brains of 3 different developmental ages: E18, P2, P5
Publication Title
Transcriptomic and anatomic parcellation of 5-HT<sub>3A</sub>R expressing cortical interneuron subtypes revealed by single-cell RNA sequencing.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 14 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
miR-182 Modulates Myocardial Hypertrophic Response Induced by Angiogenesis in Heart.
Sample Metadata Fields
Age
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Angiogenesis induced by placental growth factor (PlGF) in heart promotes myocardial hypertrophy through the paracrine action of endothelium-derived nitric oxide which triggers the degradation of RGS4 and subsequent the activation of Akt/mTORC1 pathway in cardiomyocytes. However, whether alterations in miRNAs contribute to the development of hypertrophy is largely undetermined.
Publication Title
miR-182 Modulates Myocardial Hypertrophic Response Induced by Angiogenesis in Heart.
Sample Metadata Fields
Age
View Samples