Diclofenac is a widely used analgesic drug that can cause serious adverse drug reactions. We used Saccharomyces cerevisiae as model eukaryote to elucidate the molecular mechanisms of diclofenac toxicity and resistance. Although most yeast cells died during initial diclofenac treatment, some survived and started growing again. Microarray analysis of the adapted cells identified three major processes involved in diclofenac detoxification and tolerance. Especially pleiotropic drug resistance genes and genes under control of Rlm1p, a transcription factor in the protein kinase C (PKC) pathway, were upregulated in diclofenac-adapted cells. Genes involved in ribosome biogenesis and rRNA processing were downregulated, as well as zinc-responsive genes.
Involvement of the pleiotropic drug resistance response, protein kinase C signaling, and altered zinc homeostasis in resistance of Saccharomyces cerevisiae to diclofenac.
Treatment
View SamplesAims: establishment of reference samples to investigate gene expression selective for endocrine or ductal-exocrine cells within the adult human pancreas. To this end, human islet endocrine cells, FACS-enriched in insulin+ cells, (n=3) and human exocrine ductal cells (n=2) are compared on Affymetrix HG133A platform with duplicate hybridizations of a panel of other primary human tissues.
Clusters of conserved beta cell marker genes for assessment of beta cell phenotype.
Specimen part
View SamplesAims/hypothesis: Duct cells isolated from adult human pancreas can be reprogrammed to express islet beta cell genes by adenoviral transduction of the developmental transcription factor neurogenin3 (Ngn3). In this study we aimed to fully characterize the extent of this reprogramming and intended to improve it.
Plasticity of adult human pancreatic duct cells by neurogenin3-mediated reprogramming.
Specimen part
View SamplesIn this study we conducted transcriptomics analyses of: (i) liver samples from patients suffering from acetaminophen-induced acute liver failure (n=3) and from healthy livers (n=2) and (ii) hepatic cell systems exposed to acetaminophen, including their respective vehicle controls. The investigated in vitro systems are: HepaRG cells, HepG2 cells and a novel human skinpostnatal stem cell-derived model i.e. human skin-precursors-derived hepatocyte-like cells (hSKP-HPC).
Gene expression data from acetaminophen-induced toxicity in human hepatic <i>in vitro</i> systems and clinical liver samples.
Specimen part, Disease stage, Cell line
View SamplesSaccharomyces cerevisiae flocculation occurs when fermentable sugars are limiting and is therefore considered as a way to enhance the survival chance of Flo-expressing yeast cells. In this paper, the role of Flo1p in mating was demonstrated by showing that the mating efficiency, which contributes to the increased survival rate as well by generating genetic variability, is increased when cells flocculate. This was revealed by liquid growth experiments in a low shear environment and differential transcriptome analysis of FLO1 expressing cells compared to the non-flocculent wild-type cells. The results show that a floc provides a uniquely organized multicellular ultrastructure that provides a suitable microenvironment to induce and perform cell conjugation.
Molecular mechanism of flocculation self-recognition in yeast and its role in mating and survival.
No sample metadata fields
View SamplesPremature progesterone (P) rise during GnRH antagonist cycles for IVF is a frequent phenomenon and has been associated with lower pregnancy and implantation rates. Different thresholds of progesterone have been used so far to define its premature rise during the follicular phase of an IVF stimulated cycle. In this study, we evaluated endometrial gene expression on the day of oocyte retrieval according to the level of serum progesterone on the day of hCG administration in GnRH antagonist cycles.Endometrial biopsies from eleven patients were taken with a Pipelle de Cornier (Prodimed, Neuilly-en-Thelle, France) on the day of oocyte retrieval in a GnRH antagonist/rec-FSH stimulated IVF cycle with fresh embryo transfer. Biopsies were analysed for gene expression with Affymetrix Human Genome (HG) U133 Plus 2.0 Arrays and GCOS software (Affymetrix, Santa Clara, CA, USA). Patients were divided into three different groups according to their progesterone serum concentration on the day of hCG administration (A) P <= 0.9 ng/mL, (B) 1 < P < 1.5 ng/mL, and (C) P > 1.5 ng/mL. Serum P was measured with the automated Elecsys immunoanalyser (Roche Diagnostics, Mannheim, Germany). Selected differentially expressed genes were validated with quantitative real-time PCR (QPCR) with TaqMan Gene Expression Assays (Applied Biosystems, Foster City, CA, USA).
Progesterone rise on HCG day in GnRH antagonist/rFSH stimulated cycles affects endometrial gene expression.
Specimen part
View SamplesEarly during culture of primary mouse HSCs gene expression changes.
Gene expression profiling of early hepatic stellate cell activation reveals a role for Igfbp3 in cell migration.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
No associated publication
Specimen part
View SamplesThe lower glucose-responsiveness of neonatal beta cells is generally considered a sign of endocrine immaturity. We compared mRNA profiles of neonatal and 10-weeks old rat beta cells to see how their gene expression changes with functional maturation. Neonatal beta cells showed a lower glucose-inducible increment in insulin production than adult cells. This was in part explained by basal protein synthetic hyperactivity of neonatal cells: while at 2.5mM glucose 80% of neonatal beta cells were recruited into active protein synthesis, 10 mM glucose was required to achieve a similar fraction of active adult beta cells. Besides this progressive recruitment, glucose exerted in both age groups an additional amplifying effect in the recruited cells, but clearly more so in adult beta cells that showed a higher maximal synthetic capacity/cell. Neonatal beta cells balanced an advanced endocrine differentiation as judged by their mRNA expression of conserved beta cell marker genes, with higher expression of genes involved in cell cycle and development. One example, Delta-like 1 homolog (DLK1) was used to investigate if neonatal beta cells with basal hyperactivity corresponded to a more immature subset, as marked by high DLK1. Neonatal pancreas contained distinct subsets of DLK1high and DLK1low insulin-expressing cells, but both showed equal hyperactivity. We conclude that neonatal beta cells combine advanced endocrine maturation with traits of residual developmental immaturity. If DLK1 is used as marker for the latter, the basal hyperactivity which proved to be a cardinal feature of neonatal beta cells is not a direct reflection of their residual immaturity.
Functional characteristics of neonatal rat β cells with distinct markers.
Sex, Age, Specimen part
View SamplesThe molecular determinants of a healthy human liver cell phenotype remain largely uncharacterized. In addition, the gene expression changes associated with activation of primary human hepatic stellate cells, a key event during fibrogenesis, remain poorly characterized. Here, we provide the transriptomic profile underpinning the healthy phenotype of human hepatocytes, liver sinusoidal endothelial cells (LSECs) and quiescent hepatic stellate cells (qHSCs) as well as activated HSCs (aHSCs)
Genome-wide analysis of DNA methylation and gene expression patterns in purified, uncultured human liver cells and activated hepatic stellate cells.
Sex, Age, Specimen part, Subject
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