Closure or patency of the ductus arteriosus is a critical event in neonatal life. We aimed to identify genes that are specifically expressed in the ductus arteriosus versus (the non-closing) aorta
Dlx1 and Rgs5 in the ductus arteriosus: vessel-specific genes identified by transcriptional profiling of laser-capture microdissected endothelial and smooth muscle cells.
Specimen part
View SamplesGrowth daylength, ambient CO2 level, and intracellular hydrogen peroxide (H2O2) availability all impact plant function by modulating signalling pathways, but interactions between them remain unclear. Using a whole-genome transcriptomics approach, we exploited the conditional photorespiratory nature of the catalase-deficient cat2 mutant to identify gene expression patterns responding to these three factors. Arabidopsis Col-0 and cat2 grown for 5 weeks in high CO2 in short days (SD) were transferred to air in SD or long days (LD), and microarray analysis was performed. Of more than 500 genes differentially expressed in Col-0 between high CO2 and transfer to air in SD, the response of about one-third was attenuated by transfer to air in LD. H2O2-responsive genes in cat2 were highly dependent on daylength. The majority of H2O2-induced genes were more strongly up-regulated after transfer to air in SD than to LD, while a smaller number showed an opposing pattern. Responses of other H2O2-dependent genes indicate redox-modulation of the daylength control of fundamental cell processes. The overall analysis provides evidence that (1) CO2 level modulates stress-associated gene expression; (2) both CO2 and H2O2 interact with daylength and photoreceptor signalling pathways; and (3) cellular signalling pathways may be primed to respond to increased H2O2 in a daylength-determined manner.
Day length is a key regulator of transcriptomic responses to both CO(2) and H(2)O(2) in Arabidopsis.
Specimen part, Treatment
View SamplesAbstract
Text mining of full-text journal articles combined with gene expression analysis reveals a relationship between sphingosine-1-phosphate and invasiveness of a glioblastoma cell line.
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Integrative "-Omics" Analysis in Primary Human Hepatocytes Unravels Persistent Mechanisms of Cyclosporine A-Induced Cholestasis.
Specimen part, Treatment, Time
View SamplesCyclosporine A (CsA), is an endecapeptide with strong immunosuppressant activities and has contributed significantly towards clinical progress in organ transplantation. Furthermore, it has various toxic effects in the kidney and especially in the liver where it may induce cholestasis. The CsA drug-induced cholestasis (DIC) pathway includes important genes involved in the uptake, synthesis, conjugation and secretion of bile acids, which can be verified also in hepatic models in vitro. However, whether changes in CsA-induced cholestasis pathway induced in vitro are persistent thus presenting important biomarkers for repeated dose toxicity, has not yet been investigated. We therefore performed multiple -omics analyses, including whole genome analysis of DNA methylation, gene expression and microRNA expression in primary human hepatocytes (PHH) cultured in sandwich configuration, during and after terminating CsA treatment. For this, cells were exposed to a non-cytotoxic dose of 30 M CsA daily for 3 and 5 days. To investigate the persistence of induced changes upon terminating the CsA exposure of 5 days, a subset of PHH was subjected to a washout period (WO-period) of three days. DNA methylation (using NimbleGen 2.1 deluxe promoter arrays), transcriptomic (using Affymetrix Human Genome U133 Plus 2.0 arrays) and microRNA (using Agilent Sureprint G3 Unrestricted Human miRNA V16 8 60 K microarrays) analyses were performed on days 3, 5 and 8. Identification of differentially methylated genes (DMGs), differentially expressed genes (DEGs), and differentially expressed microRNAs (DE-miRs) was performed using several R packages. DMGs, DEGs and DE-miRs were found after CsA treatment of PHH for 3 and 5 days as well after the WO-period. Interestingly, 828 persistent DEGs and 6 persistent DE-miRs, but no persistent DMGs, were found after the WO-period. These persistent DEGs and DE-miRs showed concordance for 22 genes (13 genes upregulated in gene expression and downregulated in microRNA expression; 9 genes downregulated in gene expression and upregulated in microRNA expression). Some of the persistent transcriptomic changes as well as DE-miRs could be successfully mapped onto the DIC pathway, while epigenetic changes not. Furthermore, 29 persistent DEGs in vitro showed changes in the same direction as observed in livers from cholestasis patients. None of those 29 DEGs were present in the DIC pathway or cholestasis adverse outcome pathway. We have for the first time demonstrated a persistent impact of gene expression and microRNA expression related to DIC after repeated dose administration of CsA in vitro.
Integrative "-Omics" Analysis in Primary Human Hepatocytes Unravels Persistent Mechanisms of Cyclosporine A-Induced Cholestasis.
Specimen part, Treatment, Time
View SamplesTranscript profiling of transgenic Arabidopsis thaliana seedlings constitutively overexpressing UGT74E2 (35S::UGT74E2).
Perturbation of indole-3-butyric acid homeostasis by the UDP-glucosyltransferase UGT74E2 modulates Arabidopsis architecture and water stress tolerance.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Aflatoxin B1 induces persistent epigenomic effects in primary human hepatocytes associated with hepatocellular carcinoma.
Specimen part, Disease, Compound
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Aflatoxin B1 induces persistent epigenomic effects in primary human hepatocytes associated with hepatocellular carcinoma.
Specimen part
View SamplesThe study investigated differential gene expression, microRNA expression and DNA methylation changes in a pool of primary human hepatocyte RNA and DNA following 5 days of repetitive exposure to a low (LD) or moderate (MD) dose of aflatoxin B1 or DMSO. Three biological replicates per compound/solvent.
Aflatoxin B1 induces persistent epigenomic effects in primary human hepatocytes associated with hepatocellular carcinoma.
Specimen part, Compound
View SamplesChronic exposure to aflatoxin B1 (AFB1) has, in certain regions in the world, been strongly associated with the development of hepatocellular carcinoma (HCC). AFB1 is a very potent hepatotoxic and carcinogenic mycotoxin which is frequently reported as a food contaminant. Epigenetic modifications provoked by environmental exposures, such as AFB1, may create a so called persistent "epigenetic memory" or "footprint". Deregulation of epigenetic mechanisms has actually been reported in HCC patients following AFB1 exposure; however no attempts have yet been made to investigate early effects on the epigenome level which may be persistent on longer term thereby possibly initiating carcinogenic events. In this study, we aim to identify methyl DNA-mRNA-interactions representative for a persistent epigenetic "footprint" associated with the early onset of AFB1-induced HCC. For this, primary human hepatocytes were exposed to 0.3 M of AFB1 for 5 days. Persistent epigenetic effects were m easured 3 days after terminating the carcinogenic treatment. Whole genome DNA methylation changes and whole genome transcriptomic analysis were analyzed applying microarray technologies, and cross-omics interactions were evaluated. Upon combining transcriptomics data with results on DNA methylation, a range of persistent hyper- and hypomethylated genes was identified which appeared also affected on the transcriptome level. For six of the hypomethylated and upregulated genes, namely TXNRD1, PCNA, CCNK, DIAPH3, RAB27A and HIST1H2BF, a clear role in carcinogenic events could be identified. This study is the first to report on a carcinogen-induced persistent impact on the "epigenetic footprint" in relation with the transcriptome which could be indicative for the early onset of AFB1-related development of HCC.
Aflatoxin B1 induces persistent epigenomic effects in primary human hepatocytes associated with hepatocellular carcinoma.
Specimen part
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