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GSE56998
Homo sapiens
25 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
This work focuses on understanding the molecular basis of the immune dysfunctions in Idiopathic CD4+ T cells lymphocytopenia (ICL). ICL is a rare haematological disorder of unknown origin, characterized by a profound and persistent CD4+ T-cell defect, which predisposes to life threatening opportunistic infections very similar to those seen in AIDS. To analyse more in depth the functional pathways involved in ICL pathogenesis, we conducted gene expression profiling of CD4+ T-cells isolated from blood samples from ICL, sarcoidosis and healthy individuals. Our analyses have revealed specific CD4+ T-cells gene expression signatures in ICL associated with defective TCR activation threshold, expansion of the Treg-cell compartment and interestingly with accelerated immune aging.
Publication Title
DUSP4-mediated accelerated T-cell senescence in idiopathic CD4 lymphopenia.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 16 Downloadable Samples
IlluminaHiSeq2000
Description
DNA methylation is thought to induce a transcriptional silencing through the combination of two mechanisms: the repulsion of transcriptional activators that do not recognize their binding sites when methylated, and the recruitment of transcriptional repressors that specifically bind methylated DNA. Methyl CpG Binding Domain proteins MeCP2, MBD1 and MBD2 belong to the latter category. However, the exact contribution of each protein in the DNA methylation dependent transcriptional repression occurring during development and diseases remains elusive. Here we present MBD2 ChIPseq data generated from the endogenous protein in an isogenic cellular model of human mammary oncogenic transformation. In immortalized or transformed cells, MBD2 was found in one fourth of methylated regions and associated with transcriptional silencing. Depletion of MBD2 induces upregulations of genes bound by MBD2 and methylated in their transcriptional start site regions. MBD2 was partially redistributed on methylated DNA during oncogenic transformation, independently of DNA methylation changes. Genes downregulated during this transformation preferentially gained MBD2 binding sites on their promoter. Depletion of MBD2 in transformed cells induced the upregulation of some of these repressed genes, independently of the strategy used for the abrogation of oncosuppressive barriers. Our data confirm that MBD2 is a major interpret of DNA methylation, and show an unreported dynamic in this interpretation during oncogenic transformation. Overall design: RNAseq of untreated HMEC-hTERT cells, siCtrl, siMBD2 or DAC treated HMLER cells, siCtrl or siMBD2 treated HME-ZEB1-RAS and HME-shP53-RAS cells, in duplicates.
Publication Title
Dynamics of MBD2 deposition across methylated DNA regions during malignant transformation of human mammary epithelial cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 39 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
Whole-genome expression studies in peripheral tissues of patients affected by schizophrenia (SCZ) can provide new insights into the molecular basis of the disorder and innovative biomarkers that may be of great usefulness in the clinical practice. Recent evidence suggests that skin fibroblasts could represent a non-neural peripheral model useful to investigate molecular alterations in psychiatric disorders.
Publication Title
Altered gene expression in schizophrenia: findings from transcriptional signatures in fibroblasts and blood.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage
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- 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
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