Transcriptional profiling of guard cells and mesophyll cells in response to ABA treatment
Isolation of a strong Arabidopsis guard cell promoter and its potential as a research tool.
Specimen part, Disease, Disease stage, Compound
View SamplesBiliary atresia (BA) is a rare cholestatic disease of unknown etiology that affects infants and shows an incidence of 1 out of 18,000 live births in Europe (1). The first therapeutic option is a timely performed portoenterostomy. However, the majority of patients suffer from a progressive inflammatory process, which leads to complete destruction of the extra- and intrahepatic biliary system followed by end-stage liver cirrhosis. Hence, BA is the leading indication for pediatric liver transplantation worldwide (2, 3). To understand the pathogenesis of the disease and improve theoutcome of BA patients, research has focused on the inflammatory process in liver and bile ducts, in which several factors are remarkably elevated, such as activated CD4 and CD8 T-cells, TNF alpha,IFN alpha and other proinflammatory TH1 cytokines (3-8). By the time of diagnosis, however, the disease has already reached an advanced state, characterized by the complete obstruction of the extrahepatic bile ducts with impaired bile flow and fibrosis or cirrhosis of the liver. Therefore, studies in humans focusing on the trigger mechanism of BA are limited due to the paucity of liver and availability of bile duct tissue for research. One infectious animal model has been developed, in which newborn Balb/c mice exclusively show the experimental BA phenotype after infection with rhesus rotavirus (RRV) (9, 10). This model allows the analysis of the inflammatory reactions in liver and bile ducts at early steps in the development of bile duct atresia (11-20). Furthermore, inbred mouse strains have been shown to have a different susceptibility for the development of experimental BA, suggesting that Balb/c mice have an immunological gap responsible for disease progression (10, 12). The aim of this study was to identify key genes responsible for the BA phenotype by comparing the transcriptomes at an early time point after virus infection, i.e. before bile duct atresia, between two mouse strains with different susceptibilities to BA. Differences in the virus titration and the clinical course of infected mice were analyzed, and variations in the hepatic gene response assessed by comparative microarray assays were correlated to variances in the hepatic inflammatory reaction.
Susceptibility to experimental biliary atresia linked to different hepatic gene expression profiles in two mouse strains.
Specimen part
View SamplesIn a whole-transcriptome study, cellular responses of DCs confronted with the fungi A. fumigatus, C. albicans or the bacterial cell wall component LPS were investigated. Therefore DCs of four independent donors were analyzed after 6 hours co-culture with A. fumigatus, C. albicans and LPS by Affymetrix whole genome expression arrays. In general, transcriptomic analysis revealed a clustering of the A. fumigatus and C. albicans stimulated DCs. However, LPS and fungi-dependent gene expression showed more common similarities compared to the untreated control. Stimulation with LPS induced a differential regulation of 2793 genes after 6h, while confrontation with A. fumigatus and C. albicans resulted in 743 and 974 differentially regulated genes, respectively. Kruppel-like factor 4 (KLF4) was identified as the only transcription factor that was down-regulated in DCs by both fungi but induced by stimulation with LPS.
Krüppel-like Factor 4 modulates interleukin-6 release in human dendritic cells after in vitro stimulation with Aspergillus fumigatus and Candida albicans.
Specimen part, Subject
View SamplesTo analyze the role of DNA methylation during differentiation, we performed genome-wide expression analysis of undifferentiated wild type, dnmt1-/- and triple knock out (TKO; dnmt1-/-, dnmt3a-/-, dnmt3b-/-) ESCs as well as respective embryoid bodies (EBs) at two stages of differentiation
Global DNA hypomethylation prevents consolidation of differentiation programs and allows reversion to the embryonic stem cell state.
Specimen part
View SamplesIn a whole-transcriptome study, cellular responses of DCs confronted with the fungi A. fumigatus, C. albicans or the bacterial cell wall component lipopolysaccharide (LPS) were investigated. Therefore, DCs of four independent donors were harvested after 12 hours co-culture with A. fumigatus, C. albicans and LPS and analyzed with Affymetrix whole genome expression arrays. In general, transcriptomic analysis revealed a clustering of the A. fumigatus- and C. albicans-stimulated DCs. However, LPS and fungi-dependent gene expression showed more common similarities compared to the untreated control.
Specific and Novel microRNAs Are Regulated as Response to Fungal Infection in Human Dendritic Cells.
Specimen part, Treatment, Subject
View SamplesNucleosomal incorporation of specialized histone variants is an important mechanism to generate different functional chromatin states. Here we report the identification and characterization of two novel primate-specific histone H3 variants, H3.X and H3.Y. Their mRNAs are found in certain human cell lines, in addition to several normal and malignant human tissues. In keeping with their primate-specificity, H3.X and H3.Y are detected in different brain regions. Transgenic H3.X and H3.Y proteins are stably incorporated into chromatin in a similar fashion to the known H3 variants. Importantly, we demonstrate biochemically and by mass spectrometry that endogenous posttranslationally modified H3.Y protein exists in vivo, and that stress-stimuli, such as starvation and cellular density, increase the abundance of H3.Y-expressing cells. Global transcriptome analysis revealed that knock-down of H3.Y affects cell growth and leads to changes in the expression of many genes involved in cell cycle control. Thus, H3.Y is a novel histone variant involved in the regulation of cellular responses to outside stimuli.
Identification and characterization of two novel primate-specific histone H3 variants, H3.X and H3.Y.
Cell line
View SamplesGenetic predisposition and environmental components contribute to an individuals non-alcoholic fatty liver disease (NAFLD) susceptibility. Therefore, we compared phenotypic variations of mouse strains extensively used in biomedical research during induction of high-fat diet (HFD)-mediated NAFLD and assessed transcriptional alterations in livers. In a time-resolved fashion we determined a wide spectrum of physiological parameters in C3HeB/FeJ (C3H), C57BL/6NTac, C57BL/6J, and 129P2/OlaHsd (129) males during a 7, 14, or 21 days HFD challenge and performed gene transcription analyses in steatotic livers.
Phenotypic comparison of common mouse strains developing high-fat diet-induced hepatosteatosis.
Sex, Age, Treatment
View SamplesIn this survey we effectively combined transcriptomics, proteomics and targeted-metabolomics to analyse the temporal relationship of alterations in liver preceding and accompanying the development of HFD-mediated hepatic insulin resistance. To assess HFD-mediated alterations in physiological parameters, insulin sensitivity, and molecular adaptations in liver male C3HeB/FeJ mice treated with a high-fat diet (HFD) for 7, 14, or 21 days and compared to age- matched controls fed low-fat diet (LFD).
High fat diet-induced modifications in membrane lipid and mitochondrial-membrane protein signatures precede the development of hepatic insulin resistance in mice.
Sex, Age, Treatment, Time
View SamplesMesenchymal stromal cells (MSC) are crucial components of the bone marrow (BM) microenvironment essential for regulating self-renewal, survival and differentiation of hematopoietic stem/progenitor cells (HSPC) in the stem cell niche. MSC are functionally and phenotypically altered in myelodysplastic syndromes (MDS), contributing to disease progression. MDS MSC do not harbor recurrent genetic alterations but have been shown to exhibit an altered methylome compared to MSC from healthy controls. We examined growth, differentiation and HSPC-supporting capacity of ex vivo expanded MSC from MDS patients in comparison to age-matched healthy controls after direct treatment in vitro with the hypomethylating agent azacitidine (AZA). We show that AZA exerts a direct effect on MSC by modulating their differentiation potential. Osteogenesis was significantly boosted in healthy MSC while adipogenesis was inhibited in both healthy and MDS MSC. In co-culture experiments, both AZA treated MDS MSC and healthy MSC exhibited enhanced support of non-clonal HSPC which was associated with increased cell cycle induction. Conversely, clonal MDS HSPC were inhibited by contact with AZA treated MSC. RNA-sequencing analyses of stromal cells revealed changes in pathways essential for HSPC support as well as in immune regulatory pathways. In sum, our data demonstrate that AZA treatment of stromal cells leads to upregulation of HSPC-supportive genes and cell cycle induction in co-cultured healthy HSPC, resulting in a proliferative advantage over clonal HSPC. Thus, restoration of functional hematopoiesis by AZA may be driven by activated stromal support factors in MSC providing cell cycle cues to healthy HSPC. Overall design: RNA sequencing was performed on a mesenchymal stromal cell line (EL08-1D2), either untreated or treated with Azacitidine [(-)AZA vs. (+)AZA].
Direct modulation of the bone marrow mesenchymal stromal cell compartment by azacitidine enhances healthy hematopoiesis.
Treatment, Subject
View SamplesGPAM is well characterized in triglyceride synthesis, but has never been implicated in cancer. Our study report a role for GPAM in cell migration. Gene expression changes after GPAM silencing was investigated to gain insight into possible mechanisms underlying GPAM's role in cell migration.
Glycerol-3-phosphate Acyltransferase 1 Promotes Tumor Cell Migration and Poor Survival in Ovarian Carcinoma.
Specimen part, Cell line
View Samples