Here 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 SamplesComparison of acetylcholine receptor immunization between RIIIS/J and B10.RIII mice.
Periodic gene expression program of the fission yeast cell cycle.
Specimen part
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 SamplesThis SuperSeries is composed of the SubSeries listed below.
Transcription factor TLX1 controls retinoic acid signaling to ensure spleen development.
Specimen part
View SamplesThe molecular mechanisms underlying asplenia, a condition often associated with overwhelming infections remain largely unknown. During spleen development, the transcription factor TLX1 controls morphogenesis and organ expansion, and loss of it causes spleen agenesis. However, the downstream signaling pathways that are deregulated in the absence of TLX1 are mostly unknown. Herein, we demonstrate that loss of Tlx1 in the splenic mesenchyme causes increased retinoic acid (RA) signaling. Increased RA activity causes premature differentiation of the splenic mesenchyme and reduced vasculogenesis of the splenic anlage. Moreover, excess or deficiency in RA signaling, as observed in Cyp26b1 or Rdh10 mutants respectively, also results in spleen growth arrest. Genome-wide analysis revealed that TLX1 binds RA-associated genes through the AP-1 site and cooperates with the AP-1 family transcription factors to regulate transcription. Pharmacological inhibition of RA signaling partially rescues the spleen defect. These findings establish the critical role of TLX1 in controlling RA metabolism, and provide novel mechanistic insights into the molecular determinants underlying congenital asplenia.
Transcription factor TLX1 controls retinoic acid signaling to ensure spleen development.
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 SamplesBACKGROUND. Human prostate cancer LNCaP and PC-3 cell lines have been extensively used as prostate cancer cell models to study prostate cancer progression and to develop therapeutic agents. Although LNCaP and PC-3 cells are generally assumed to represent early and late stages of prostate cancer development, respectively, there is limited information regarding comprehensive gene expression patterns between these two cells lines and relating these cells to prostate cancer progression based on their gene expression.
Unique patterns of molecular profiling between human prostate cancer LNCaP and PC-3 cells.
No sample metadata fields
View SamplesAnalysis of gene expression at RNA level by 4 different cell sorted Vg9Vd2 subsets (Subset 1=CD28+CD27+, Subset2=CD28-CD27+, Subset 3=CD28-CD7-CD16-, Subset 4 = CD28-CD27-CD16+). Results highlight differences in RNA expression characterising these four cell populations into distinct phenotypic subsets with distinct functional potential
Heterogeneous yet stable Vδ2(+) T-cell profiles define distinct cytotoxic effector potentials in healthy human individuals.
Specimen part
View Samples