The miR-17-92 microRNA cluster is often activated in cancer cells, but the identity of its targets remains largely elusive. Here we examined the effects of activation of the entire miR-17-92 cluster on global protein expression in neuroblastoma cells.
The miR-17-92 microRNA cluster regulates multiple components of the TGF-β pathway in neuroblastoma.
Specimen part
View SamplesHypermethylation of tumor suppressor gene (TSG) promoters confers growth advantages to cancer cells, but how these changes arise is poorly understood. Here, we report that tumor hypoxia reduces the activity of oxygen-dependent TET enzymes, which catalyze DNA de-methylation through 5-methylcytosine oxidation. This occurs independently of hypoxia-associated alterations in TET gene expression, basal metabolism, HIF activity or nuclear reactive oxygen species, but directly depends on oxygen shortage. Hypoxia-induced loss of TET activity increases hypermethylation at gene promoters in vitro, while also in patients, gene promoters are markedly more methylated in hypoxic than normoxic tumors. Affected genes are frequently involved in DNA repair, cell cycle regulation, angiogenesis and metastasis, indicating cellular selection of hypermethylation events. Overall, up to 50% of the tumor-associated hypermethylation is ascribable to hypoxia across various cancer types. Accordingly, spontaneous murine breast tumors become hypermethylated when rendered hypoxic through vessel pruning, whereas vessel normalisation rescues this effect. Tumor hypoxia thus acts as a novel regulator underlying DNA methylation. Overall design: RNAseq of MCF7 cells grown under hypoxic and normoxic conditions. Submission includes data on 5 independent RNAseq experiments, each containing biological replicates grown under hypoxic conditions (0.5% oxygen), and under normoxic conditions.
Tumour hypoxia causes DNA hypermethylation by reducing TET activity.
Subject
View SamplesWe sequenced mRNA extracted from heads of a D. melanogaster population that was sedated with a stream of ethanol saturated vapor, 30 minutes before RNA extraction; and from an age-matched untreated control group. Differential gene expression between the two groups was calculated and reported. Overall design: Examination of mRNA levels in heads of D. melanogaster adult females after ethanol exposure was performed using next generation sequencing (NGS) technology.
Alcohol resistance in Drosophila is modulated by the Toll innate immune pathway.
Cell line, Treatment, Subject
View SamplesChoroid plexuses (CP) develop early during development. They form a barrier between the blood and the cerebrospinal fluid, and fulfill important protective and nutritive functions. We used Affymetrix microarrays to assess whether CP of the lateral ventricles (LVCP) have similar functions in developing and adult brain. We identified distinct families of protective and transport genes and found that most of these genes were already well expressed during development.
Developmental changes in the transcriptome of the rat choroid plexus in relation to neuroprotection.
Specimen part
View SamplesRNA from circulating blood reticulocytes was utilized to provide a robust description of genes transcribed at the final stages of erythroblast maturation. After depletion of leukocytes and platelets, Affymetrix HG-U133 arrays were hybridized with probe from total RNA isolated from blood sampled from 14 umbilical cords and 14 healthy adult humans.
The human reticulocyte transcriptome.
No sample metadata fields
View SamplesHuman ES or iPS Cells were differentiated into endothelial cells (ECs) defined by expression of CD31 (PECAM1) and CD144 (VE-Cadherin) on the cell surface. All ES or iPS derived ECs were greater than 90% double positive for these two markers.
Limited gene expression variation in human embryonic stem cell and induced pluripotent stem cell-derived endothelial cells.
Specimen part
View SamplesSatellite cells are the primary source of stem cells for skeletal muscle growth and regeneration. Since adult stem cell maintenance involves a fine balance between intrinsic and extrinsic mechanisms, we performed genome-wide chronological expression profiling to identify the transcriptomic changes involved during early postnatal growth till acquisition of satellite cell quiescence.
Pericytes in the myovascular niche promote post-natal myofiber growth and satellite cell quiescence.
Specimen part
View Samplesdifferential expression between wild-type pistils of Arabidopsis thaliana at late 11 to late 12 floral stages, and similar stage pistils of coatlique mutant which lacks a functional embryo sac
Genetic subtraction profiling identifies genes essential for Arabidopsis reproduction and reveals interaction between the female gametophyte and the maternal sporophyte.
Specimen part
View SamplesmESCs cultured in microfluidic chambers secrete endogneous signals which accumulate to facilitate expression of pluripotency associated genes
Embryonic Stem Cells Cultured in Microfluidic Chambers Take Control of Their Fate by Producing Endogenous Signals Including LIF.
Cell line
View SamplesTo study the effect of structural changes on expression, we assessed gene expression in genomic disorder mouse models. Both a microdeletion and its reciprocal microduplication mapping to mouse chromosome 11 (MMU11), which model the rearrangements present in Smith-Magenis (SMS) and Potocki-Lupski (PTLS) syndromes patients, respectively, have been engineered. We profiled the transcriptome of five different tissues affected in human patients in mice with 1n (Deletion/+), 2n (+/+), 3n (Duplication/+) and uniallelic 2n (Deletion/Duplication) copies of the same region in an identical genetic background. The most differentially expressed transcripts between the four studied genotypes were ranked. A highly significant propensity, are mapping to the engineered SMS/PTLS interval in the different tissues. A statistically significant overrepresentation of the genes mapping to the flanks of the engineered interval was also found in the top-ranked differentially expressed genes. A phenomenon efficient across multiple cell lineages and that extends along the entire length of the chromosome, tens of megabases from the breakpoints. These long-range effects are unidirectional and uncoupled from the number of copies of the copy number variation (CNV) genes. Thus, our results suggest that the assortment of genes mapping to a chromosome is not random. They also indicate that a structural change at a given position of the human genome may cause the same perturbation in particular pathways regardless of gene dosage. An issue that should be considered in appreciating the contribution of this class of variation to phenotypic features.
Phenotypic consequences of copy number variation: insights from Smith-Magenis and Potocki-Lupski syndrome mouse models.
Sex
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