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 SamplesMegakaryoblastic Leukemia 1 and 2 (MKL1 and 2) are coactivators of the transcription factor Serum Response Factor (SRF). We recently showed that depletion of MKL1 and 2 abolished HCC xenograft growth, associated with oncogene-induced senescence. To identify suitable MKL target genes mediating these effects, we performed microarray analyses using HuH7 hepatocellular carcinoma cells stably expressing shRNA against MKL1/2 (HuH7 MKL1/2 KD). We therefore used a Affymetrix oligonucleotide array and filtered for genes whose expression in HuH7 MKL1/2 KD cells was reduced by a factor of at least 2.5 as compared to control HuH7 cells.
The novel MKL target gene myoferlin modulates expansion and senescence of hepatocellular carcinoma.
Specimen part
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 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 SamplesAims: We investigate sex differences and the role of oestrogen receptor beta (ERbeta) in a mouse model of pressure overload-induced myocardial hypertrophy. Methods and results: We performed transverse aortic constriction (TAC) or sham surgery in male and female wild-type (WT) and ERbeta knockout (ERbeta-/-) C57Bl6 mice. All mice were characterised by echocardiography and haemodynamic measurements and were sacrificed nine weeks after surgery. Left ventricular (LV) samples were analysed by microarray profiling, real-time RT-PCR and histology. After nine weeks, WT males showed more hypertrophy and heart failure signs than WT females. Notably, WT females developed a concentric form of hypertrophy, while males developed eccentric hypertrophy. These sex differences were abolished in ERbeta-/- mice. ERbeta deletion augmented the TAC-induced increase in cardiomyocyte diameter in both sexes. Gene expression profiling revealed that male WT hearts had a stronger induction of matrix-related genes and a stronger repression of mitochondrial genes than female hearts. ERbeta-/- mice exhibited a different transcriptome. Induction of pro-apoptotic genes after TAC occurred in ERbeta-/- mice of both sexes with a stronger expression in ERbeta-/- males. Histological analysis revealed, that cardiac fibrosis was more pronounced in male WT TAC than in female mice. This was abolished in ERbeta-/- mice. Apoptosis was significantly induced in both sexes of ERbeta-/- TAC mice, but it was most prominent in males. Conclusion: Female sex offers protection against ventricular chamber dilation in the TAC model. Both the female sex and ERbeta attenuate the development of fibrosis and apoptosis; thus slowing the progression to heart failure.
Female sex and estrogen receptor-beta attenuate cardiac remodeling and apoptosis in pressure overload.
Sex, Age, Specimen part
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 SamplesPressure overload (PO) leads first to cardiac hypertrophy and later to heart failure. In mice, PO leads to sex differences in cardiac morphology and function. However, early sex differences in gene regulation that precede sex differences in function have not yet been identified.
Sex-specific pathways in early cardiac response to pressure overload in mice.
Sex
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.
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