T-cell clones were obtained by limiting dilution culture of PBMC of HTLV-1 carriers. Exon expression profiling was performed using Affymetrix exon array (Affymetrix Human Exon 1.0 ST Array) according to the manufacturer's instructions. Gene version of CEL files 01 to 12 are presented in GSE46518.
HTLV-1-infected CD4+ T-cells display alternative exon usages that culminate in adult T-cell leukemia.
Specimen part
View SamplesT-cell clones were obtained by limiting dilution culture of PBMC of HTLV-1 carriers. Exon expression profiling was performed using Affymetrix exon array (Affymetrix Human Exon 1.0 ST Array) according to the manufacturer's instructions.
HTLV-1 bZIP factor HBZ promotes cell proliferation and genetic instability by activating OncomiRs.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
A stemness-related ZEB1-MSRB3 axis governs cellular pliancy and breast cancer genome stability.
Specimen part, Cell line
View SamplesAberrant cell proliferation, a hallmark of most cancers, requires the escape from intrinsic antitumour barriers. Primary among these is the DNA damage response (DDR). In both cell culture-models and in early stages of tumorigenesis in vivo, activated oncogenes induce DNA replication stress and DNA double-strand breaks (DSBs), leading to DDR activation and p53-dependent apoptosis and/or senescence. The means by which tumour-initiating cells, also termed cancer stem cells (CSCs), circumvent this oncosuppressive response is unknown. Here we demonstrate that the ZEB1 transcription factor provides breast CSCs with the ability to withstand an aberrant mitogenic activity. Its forced expression in human mammary epithelial cells is sufficient to alleviate DNA replicative stress and to decrease the production of reactive oxygen species, an important contributor to DDR and oncogene-induced senescence. Consistently, human breast cancer cells with endogenous ZEB1 expression show two characteristic features: low levels of DSBs and DDR markers, reflecting mitigation of the DNA replication stress, and a low p53 mutation frequency, reflecting a weak selective pressure for inactivation. Using high-throughput sequencing analysis of controlled cellular models, we further demonstrate that ZEB1 delays the onset of structural chromosomal instability (CIN), a known consequence of replicative stress and prevents the emergence of chromosome 8p deletions and 8q amplifications, two prevalent abnormalities in high-grade breast cancers. Supporting these findings, ZEB1 expression discriminates human breast tumours by their copy number alterations (CNAs) and chromosome 8 aberrations. We propose that the tumorigenic potential of CSCs relies upon their unique capacity to tolerate oncogenic stimuli through the alleviation of DNA replication stress.
A stemness-related ZEB1-MSRB3 axis governs cellular pliancy and breast cancer genome stability.
Specimen part
View SamplesRNA-SEQ of mutants B cell for IgH 3''RR and Emu Overall design: CD43- splenic B-cells from wt, Eµ-deficient or 3''RR deficient mice, non stimulated (NS) or stimulated (S) with 5mg/ml LPS.
E<sub>μ</sub> and 3'RR IgH enhancers show hierarchic unilateral dependence in mature B-cells.
No sample metadata fields
View SamplesPurpose: mRNA translation into protein is highly regulated, but the role of mRNA isoforms, noncoding RNAs (ncRNAs), and genetic variants has yet to be systematically studied. Using high-throughput sequencing (RNA-seq), we have measured cellular levels of mRNAs and ncRNAs, and their isoforms, in lymphoblast cell lines (LCL) and in polysomal fractions, the latter shown to yield strong correlations of mRNAs with expressed protein levels. Analysis of allelic RNA ratios at heterozygous SNPs served to reveal genetic factors in ribosomal loading. Methods: RNA-seq was performed on cytosolic extracts and polysomal fractions (3 ribosomes or more) from three lymphoblastoid cell lines. As each RNA fraction was amplified (NuGen kit), and relative contributions from various RNA classes differed between cytosol and polysomes, the fraction of any given RNA species loaded onto polysomes was difficult to quantitate. Therefore, we focused on relative recovery of the various RNA classes and rank order of single RNAs compared to total RNA. Results: RNA-seq of coding and non-coding RNAs (including microRNAs) in three LCLs revealed significant differences in polysomal loading of individual RNAs and isoforms, and between RNA classes. Moreover, correlated distribution between protein-coding and non-coding RNAs suggests possible interactions between them. Allele-selective RNA recruitment revealed strong genetic influence on polysomal loading for multiple RNAs. Allelic effects can be attributed to generation of different RNA isoforms before polysomal loading or to differential loading onto polysomes, the latter defining a direct genetic effect on translation. Several variants and genes identified by this approach are also associated with RNA expression and clinical phenotypes in various databases. Conclusions: These results provide a novel approach using complete transcriptome RNA-seq to study polysomal RNA recruitment and regulatory variants affecting protein translation. Overall design: cells from 3 samples were grown to 5x105 cells/mL density in T75 tissue culture flask and harvested, total RNA and polysome bound RNA was sequenced by Ion Proton
Allele-Selective Transcriptome Recruitment to Polysomes Primed for Translation: Protein-Coding and Noncoding RNAs, and RNA Isoforms.
No sample metadata fields
View SamplesGene expression analysis of three sets of patient-derived T-ALL xenografted murine lines treated or not treated with Givinostat, to investigate the immediate anti-leukemic effects after 6 hours of in vivo treatment with this histone deacetylase inhibitor.
An immediate transcriptional signature associated with response to the histone deacetylase inhibitor Givinostat in T acute lymphoblastic leukemia xenografts.
Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
KAP1 regulates gene networks controlling T-cell development and responsiveness.
Specimen part
View SamplesThe modulation of chromatin status at specific genomic loci controls lymphoid differentiation. Here, we investigated the role played in this process by KAP1, the universal cofactor of KRAB-containing Zinc Finger Proteins (KRAB-ZFPs), a tetrapod-restricted family of transcriptional repressors. T cell-specific Kap1 knockout mice displayed a significant expansion of immature thymocytes and imbalances in the ratios of mature T cells in the thymus and the spleen, with impaired responses to TCR stimulation. Transcriptome and chromatin studies revealed that KAP1 directly controls the expression of a number of genes involved in TCR and cytokine signalling, among which Traf1 and FoxO1, and is strongly associated with cis-acting regulatory elements marked by the H3K9me3 repressive mark on the genome of thymic T cells. Likely responsible for tethering KAP1 to at least part of its genomic targets, a small number of KRAB/ZFPs are selectively expressed in T lymphoid cells. These results reveal the so far unsuspected yet important role of KRAB/KAP1-mediated epigenetic regulation in T lymphocyte differentiation and activation.
KAP1 regulates gene networks controlling T-cell development and responsiveness.
No sample metadata fields
View SamplesExperiment to understand relationships between sheep rumen wall transcriptome and microbial methane emissions Overall design: RNA seq of ventral rumen wall of Australian sheep
Across-Experiment Transcriptomics of Sheep Rumen Identifies Expression of Lipid/Oxo-Acid Metabolism and Muscle Cell Junction Genes Associated With Variation in Methane-Related Phenotypes.
Subject
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