This SuperSeries is composed of the SubSeries listed below.
Gene expression classification of colon cancer into molecular subtypes: characterization, validation, and prognostic value.
Sex
View SamplesFrom a clinical and molecular perspective, colon cancer (CC) is a heterogeneous disease but to date no classification based on high-density transcriptome data has been established. The aim of this study was to build up a robust molecular classification ofmRNA expression profiles (Affymetrix U133Plus2) ofa large series of 443 CC and 19 non-tumoral colorectal mucosas, and to validate it on an independent serie of 123 CC and 906 public dataset.We identified and validated six molecular subtypes in this large cohort as a combination of multiple molecular processes that complement current disease stratification based on clinicopathological variables and molecular markers. The biological relevance of these subtypes was consolidated by significant differences in survival. These insights open new perspectives for improving prognostic models and targeted therapies.
Gene expression classification of colon cancer into molecular subtypes: characterization, validation, and prognostic value.
Sex
View SamplesHere we studied the effects of anticonvulsant drug exposure in a human embryonic stem cell (hESC) based neuro- developmental toxicity test (hESTn). During neural differentiation the cells were exposed, for either 1 or 7 days, to non-cytotoxic concentration ranges of valproic acid (VPA) or carbamazepine (CBZ), anti-epileptic drugs known to cause neurodevelopmental toxicity.
Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay.
Time
View SamplesZebrafish embryos have been proposed as an attractive alternative model system for hepatotoxicity testing.
A transcriptomics-based hepatotoxicity comparison between the zebrafish embryo and established human and rodent in vitro and in vivo models using cyclosporine A, amiodarone and acetaminophen.
Compound
View SamplesIn acute promyelocytic leukemia (APL), differentiation therapy with all-trans retinoic acid (ATRA)
Chemokine induction by all-trans retinoic acid and arsenic trioxide in acute promyelocytic leukemia: triggering the differentiation syndrome.
Specimen part
View SamplesWT J1 and 3B3L cells (in which Dnmt3B and Dnm3L are constitutively expressed from an exogenous construct) were cultured under both serum/LIF and 2i/LIF conditions. 3B3L cells do not show ground state-associated hypomethylation phenotype. This experiment sought to analyse the gene expression changes between the two conditions. Overall design: Three biological replicates per condition J1 serum, J1 2i, 3B3-3l serum, 3B3-3l 2i.
DNA Methylation Directs Polycomb-Dependent 3D Genome Re-organization in Naive Pluripotency.
Specimen part, Cell line, Subject
View SamplesTFIID is a central player in activated transcription initiation. Recent evidence suggests that the role and composition of TFIID is more diverse than previously understood. To investigate the effects of changing the composition of TFIID in a simple system we depleted TAF1 from Drosophila cells and determined the consequences on metal induced transcription at an inducible gene, Metallothionein B (MtnB). We observe a marked increase in the levels of both the mature message and pre-mRNA in TAF1 depleted cells. Under conditions of continued metal exposure, we show that TAF1 depletion increases the magnitude of the initial transcription burst, but has no effect on the timing of that burst. We also show that TAF1 depletion causes delay in the shut-off of transcription upon removal of the stimulus. Thus TAFs are involved in both establishing an upper limit of transcription during induction and efficiently turning the gene off once the inducer is removed. Using genomewide nascent-seq we identify hundreds of genes that are controlled in a similar manner indicating that the findings at this inducible gene are likely generalizable to a large set of promoters. There is a long-standing appreciation for the importance of the spatial and temporal control of transcription. Here we uncover an important third dimension of control, the magnitude of the response. Our results show that the magnitude of the transcriptional response to the same signaling event, even at the same promoter, can vary greatly depending on the composition of the TFIID complex in the cell. Overall design: Nascent RNA was sequenced from replicate samples of Drosophila S2 cells treated with double-stranded RNA directed against E. coli LacI (Control) or against Drosophlia TAF1 (experimental). Reads per kilo-base per million (RPKM) was determined for each gene and the control and experimental samples were compared to determine the genes that were affected by the depletion of TAF1.
Holo-TFIID controls the magnitude of a transcription burst and fine-tuning of transcription.
Specimen part, Subject
View SamplesTo identify MBNL1-dependent changes in gene expression, MDA-MB-231 cells expressing either control or MBNL1-targeting shRNAs were transcriptomically profiled. Overall design: MDA-MB-231 cells stably expressing a control or two independent MBNL1-targeting shRNAs were sequenced in biological duplicate.
Muscleblind-like 1 suppresses breast cancer metastatic colonization and stabilizes metastasis suppressor transcripts.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Cell-autonomous function of Runx1 transcriptionally regulates mouse megakaryocytic maturation.
Specimen part
View SamplesRUNX1 transcription factor (TF) is a key regulator of megakaryocytic development and when mutated is associated with familial platelet disorder and predisposition to acute myeloid leukemia (FPD-AML). We used mice lacking Runx1 specifically in megakaryocytes (MKs) to characterize the Runx1-mediated transcriptional program during advanced stages of MK differentiation. Gene expression and chromatin-immunoprecipitation-sequencing (ChIP-seq) of Runx1 andp300identified functional Runx1-bound MK enhancers. Runx1/p300 co-bound regions showed significant enrichment in genes important for MK and platelet homeostasis. Runx1-bound regions were highly enriched in RUNX and ETS motifs and to a lesser extent in GATA motif.The data providesthe first example of genome-wide Runx1/p300 occupancy in maturating FL-MK,unravels the Runx1-regulated program controlling MK maturationin vivoandidentifies itsbona fideregulated genes. It advances our understandingof the molecular events that upon mutations in RUNX1 lead to thepredisposition to familial platelet disorders and FPD-AML.
Cell-autonomous function of Runx1 transcriptionally regulates mouse megakaryocytic maturation.
Specimen part
View Samples