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GSE9200
Homo sapiens
28 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We have developed a nonheuristic genome topography scan (GTS) algorithm to characterize the patterns of genomic alterations in human glioblastoma (GBM), identifying frequent p18INK4C and p16INK4A codeletion. Functional reconstitution of p18INK4C in GBM cells null for both p16INK4A and p18INK4C resulted in impaired cell-cycle progression and tumorigenic potential. Conversely, RNAi-mediated depletion of p18INK4C in p16INK4A-deficient primary astrocytes or established GBM cells enhanced tumorigenicity in vitro and in vivo. Furthermore, acute suppression of p16INK4A in primary astrocytes induced a concomitant increase in p18INK4C. Together, these findings uncover a feedback regulatory circuit in the astrocytic lineage and demonstrate a bona fide tumor suppressor role for p18INK4C in human GBM wherein it functions cooperatively with other INK4 family members to constrain inappropriate proliferation.
Publication Title
Feedback circuit among INK4 tumor suppressors constrains human glioblastoma development.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 28 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We have developed a nonheuristic genome topography scan (GTS) algorithm to characterize the patterns of genomic alterations in human glioblastoma (GBM), identifying frequent p18INK4C and p16INK4A codeletion. Functional reconstitution of p18INK4C in GBM cells null for both p16INK4A and p18INK4C resulted in impaired cell-cycle progression and tumorigenic potential. Conversely, RNAi-mediated depletion of p18INK4C in p16INK4A-deficient primary astrocytes or established GBM cells enhanced tumorigenicity in vitro and in vivo. Furthermore, acute suppression of p16INK4A in primary astrocytes induced a concomitant increase in p18INK4C. Together, these findings uncover a feedback regulatory circuit in the astrocytic lineage and demonstrate a bona fide tumor suppressor role for p18INK4C in human GBM wherein it functions cooperatively with other INK4 family members to constrain inappropriate proliferation.
Publication Title
Feedback circuit among INK4 tumor suppressors constrains human glioblastoma development.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 32 Downloadable Samples
Illumina HiSeq 4000
Description
Some neuropsychiatric disease, including schizophrenia, may originate during prenatal development, following periods of gestational hypoxia and placental oxidative stress. Here we investigated if gestational hypoxia promotes damaging secretions from the placenta that affect fetal development and whether a mitochondria-targeted antioxidant MitoQ might prevent this. Gestational hypoxia caused low birth-weight and changes in young adult offspring brain, mimicking those in human neuropsychiatric disease. Exposure of cultured neurons to fetal plasma or to secretions from the placenta or from model trophoblast barriers that had been exposed to altered oxygenation caused similar morphological changes. The secretions and plasma contained altered microRNAs whose targets were linked with changes in gene expression in the fetal brain and with human schizophrenia loci. Molecular and morphological changes in vivo and in vitro were prevented by a single dose of MitoQ bound to nanoparticles, which were shown to localise and prevent oxidative stress in the placenta but not in the fetus. We suggest the possibility of developing preventative treatments that target the placenta and not the fetus to reduce risk of psychiatric disease in later life. Overall design: 16 samples (4 biological replicates per group) were analysed using RNA sequencing. The 4 groups were: Normoxia+Saline (control sample), Normoxia+MitoQ-NP, Hypoxia+Saline and Hypoxia+MitoQ-NPs. Pair-wise comparison between all groups was performed.
Publication Title
Treating the placenta to prevent adverse effects of gestational hypoxia on fetal brain development.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 16 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
RNA-Seq analysis of atypical chronic myeloid leukemia samples Overall design: We sequenced leukemic mRNA from 13 Atypical Cronic Mieloid Leukemia (aCML) samples by Illumina GAIIx. Transcriptomic profiles, differentially expressed genes and pathway enrichment analysis were obtained comparing 7 SETBP1-mutated samples and 6 non-mutated (WT) samples by using TopHat aligner and SAMMate gene expression quantifier. We focused on the gene expression profile of known coding transcripts. A dataset of 20,907 protein-coding Ensembl Genes was obtained from the RNA-Seq by using the Human Ensembl GTF annotation file vs54 dowloaded from ftp://ftp.ensembl.org/pub/release-54/gtf/homo_sapiens/.
Publication Title
Recurrent SETBP1 mutations in atypical chronic myeloid leukemia.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A heterozygous IDH1R132H/WT mutation induces genome-wide alterations in DNA methylation.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
The cytosolic NADP+-dependent isocitrate dehydrogenase IDH1 is frequently mutated in human cancers. Recent studies have shown that IDH1 mutant primary glioblastomas (GBM) and acute myeloid leukemias (AML) display robust association with CpG island methylator phenotype (CIMP). Such observations bring into question whether IDH1 mutations directly contribute to the development of CIMP or if the hypermethylation phenotype precedes acquisition of IDH1 mutations. To reveal the effects of IDH1 mutations on DNA methylation and gene expression, we introduced the most frequently observed IDH1 mutation, R132H, into a human cancer cell line through gene targeting. We profiled changes in methylation at over 27,000 CpG dinucleotides spanning 14,475 unique gene regions and characterized genome-wide gene expression alterations resulting from IDH1R132H knockin. We observed consistent changes in both DNA methylation and gene expression when comparing two independent IDH1R132H knockin clones to their wild-type parent, and report hypermethylation of over 2,000 loci, the majority of which contained preexisting methylation in IDH1WT parental cells. These loci exhibit the same trend in primary TCGA glioblastoma tumors with mutant IDH1 as compared to those with wild-type IDH1 and have significant overlap with genes hypermethylated in glioma-CIMP+ tumors. Furthermore, we identify specific DNA methylation and gene expression alterations which correlate with IDH1 mutations in our cell-line model as well as primary glioblastomas, including hypermethylation and transcriptional silencing of RBP1. The presented data provide insight on epigenetic alterations induced by IDH1 mutations and support a contributory role for IDH1 mutants in regulation of DNA methylation and gene expression in human cancer cells.
Publication Title
A heterozygous IDH1R132H/WT mutation induces genome-wide alterations in DNA methylation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
MiR-33a is involved in the maintenance of Glioma Initiating Cells (GIC) and tumor progression. MicroRNA-33a could promote GIC growth and self-renewal by regulating two pathways including cAMP/PKA pathway and Notch pathway. We used microarrays to identify the direct target genes of miR-33a in a glioblastoma cell line D456MG.
Publication Title
miR-33a promotes glioma-initiating cell self-renewal via PKA and NOTCH pathways.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 14 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Mouse neural stem cells were generated from conditional knockout mice (Cicflox/flox) or the wild trype control mice (Cic+/+). Cic is conditionally knocked out following expression of Cre-recombinase. Cre-recombinase was incorporated in vitro via adenoviral-Cre transduction.
Publication Title
<i>Cic</i> Loss Promotes Gliomagenesis via Aberrant Neural Stem Cell Proliferation and Differentiation.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- IlluminaHiSeq2000
Description
Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults, with glioma initiating cells (GICs) implicated to be critical for tumor progression and resistance to therapy. KDM1B is involved in regulating GICs'' responses to hypoxia, since over-expression of KDM1B delays the cell growth under hypoxia while knocking-down of KDM1B in GICs promotes their survival and tumorigenic abilities. Overall design: We used RNA-Sequencing to detail the global change of gene expression in GICs with knockdown of KDM1B, and identified de-regulated genes and pathways downstream of KDM1B. CD133+ D456MG GICs were infected with non-targeting control and shRNA of KDM1B. Then RNA was extracted and gene expression was profiled by RNA-Seq.
Publication Title
MiR-215 Is Induced Post-transcriptionally via HIF-Drosha Complex and Mediates Glioma-Initiating Cell Adaptation to Hypoxia by Targeting KDM1B.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Mouse neural stem cells were generated from conditional knock-in mice. Mutant IDH1 is conditionally expressed following expression of Cre-recombinase. Cre-recombinase was incorporated in vitro
Publication Title
Mutant IDH1 Disrupts the Mouse Subventricular Zone and Alters Brain Tumor Progression.
Sample Metadata Fields
Specimen part
View Samples