Idiosyncratic drug reactions (IDRs) cause significant morbidity and mortality. In an animal model of IDRs, 50-80% of Brown Norway rats exposed to D-penicillamine develop an autoimmune syndrome after several weeks of treatment. The symptoms of the IDR are similar to that observed in humans who take D-penicillamine. The mechanism of this reaction is unknown, and no effective biomarkers have been identified to predict susceptibility. We postulate that cell stress caused by drugs is required to initiate the response. We used a highthroughput approach to identify factors that might represent danger signals by profiling hepatic gene expression 6 h after dosing with D-penicillamine (150 mg/kg). Our results show that the drug-treated animals cluster into two distinct groups. One group exhibits substantial expression changes relative to control animals. The most significantly altered transcripts have a role in stress, energy metabolism, acute phase response, and inflammation. We used quantitative reverse transcriptase polymerase chain reaction to measure transcript levels in liver biopsies of 33 rats and found that resistant animals cluster together. This 'resistant' cluster of animals contains 87.5% (7/8) resistant animals but only 48% (12/25) 'sensitive' animals. This separation is statistically significant at the p 0.01 level.
Gene expression profiling in a model of D-penicillamine-induced autoimmunity in the Brown Norway rat: predictive value of early signs of danger.
Sex, Specimen part, Treatment
View SamplesThis study aimed to understand the transcriptional networks regulating endoderm specification from HESC and therefore explored the phenotype of CA1 and CA2 HESC constitutively over-expressing SOX7 or SOX17. Cell lines were created using an inducible construct whereby clonal populations containing transgene integration are selected by Neomycin resistance without expressing of the gene of interest (NoCre controls). Transgene expression is induced via Cre-mediated recombination and selected for puromycin resistance (SOX O/E). The phenotype of the resulting cells suggests that SOX7 expressing HESC represent stable extraembryonic endoderm progenitors, while SOX17 expressing HESC represent early definitive endoderm progenitors. Both in vitro and in vivo SOX7 expressing HESC are restricted to the extraembryonic endoderm lineage, while SOX17 expressing HESC demonstrate mesendodermal specificity. In vitro, SOX17 expressing HESC efficiently produce mature definitive endoderm derivatives.
Establishment of endoderm progenitors by SOX transcription factor expression in human embryonic stem cells.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Expression profiling and functional analysis of Populus WRKY23 reveals a regulatory role in defense.
Specimen part
View SamplesTo investigate the function of poplar WRKY23, we generated PtWRKY23-overexpressing and -underexpressing (RNAi) plants. Transgenic plants were inoculated with Melampsora rust or mock-inoculated for assessment of rust-resistance and for gene expression profiling using the poplar Affymetrix GeneChip to study the consequences of PtWRKY23 overexpression and underexpression. Transcriptome analysis of PtWRKY23 overexpressors revealed a significant overlap with the Melampsora-infection response. Transcriptome analysis also indicated that PtWRKY23 affects redox homeostasis and cell wall-related metabolism.
Expression profiling and functional analysis of Populus WRKY23 reveals a regulatory role in defense.
Specimen part
View SamplesTo investigate the function of poplar WRKY23, we generated PtWRKY23-overexpressing and -underexpressing (RNAi) plants. Transgenic plants were inoculated with Melampsora rust or mock-inoculated for assessment of rust-resistance and for gene expression profiling using the poplar Affymetrix GeneChip to study the consequences of PtWRKY23 overexpression and underexpression. Transcriptome analysis of PtWRKY23 overexpressors revealed a significant overlap with the Melampsora-infection response. Transcriptome analysis also indicated that PtWRKY23 affects redox homeostasis and cell wall-related metabolism.
Expression profiling and functional analysis of Populus WRKY23 reveals a regulatory role in defense.
Specimen part
View SamplesMany reports show an association between the Pst system, the Pho regulon related genes and bacterial virulence. Our previous results showed that a functional Pst system is required for full virulence, resistance to serum, polymyxin B and acid shock. However, the interplay between the Pst system and virulence has an unknown molecular basis. To understand global APEC virulent strain responses to Pho regulon activation, we conducted transcriptome profiling experiments comparing the APEC chi7122 strain and its isogenic Pst mutant grown in rich phosphate medium using the Affymetrix GeneChip E. coli Genome 2.0 Array. The Affymetrix GeneChip E. coli Genome 2.0 Array contains the genome of the E. coli MG1655 and three pathogenic E. coli strain (EDL933, Sakai and CFT073) representing 20,366 genes. While comparing genes expression between Pst mutant and the wild type chi7122 strain, 471 genes are either up- (254) or down-regulated (217) of at least 1.5-fold, with a p-value inferior or equal to 0.05 and a false discovery rate of 2.71%.
Genome-wide transcriptional response of an avian pathogenic Escherichia coli (APEC) pst mutant.
No sample metadata fields
View SamplesXEN cells are derived from the primitive endoderm of mouse blastocysts. In culture and in chimeras they exhibit properties of parietal endoderm. However, BMP signaling promotes XEN cells to form an epithelium and differentiate into visceral endoderm (VE). Of the several different subtypes of VE described, BMP induces a subtype that is most similar to the VE adjacent to the trophoblast-derived extraembryonic ectoderm.
BMP signaling induces visceral endoderm differentiation of XEN cells and parietal endoderm.
Treatment
View SamplesFAN (Factor associated with neutral sphingomyelinase activation) is an adaptor protein that constitutively binds to TNF-R1. Microarray analysis was performed in fibroblasts derived from wild-type or FAN knockout mouse embryos to evaluate the role of FAN in TNF-induced gene expression.
FAN stimulates TNF(alpha)-induced gene expression, leukocyte recruitment, and humoral response.
Treatment
View Samples