About 10% of all NSCLC patients respond to gefitnib treatment and all of these patients will acquire resistance to the EGFR TKI.
Rapidly acquired resistance to EGFR tyrosine kinase inhibitors in NSCLC cell lines through de-repression of FGFR2 and FGFR3 expression.
Cell line, Treatment
View SamplesA new method for amplification and labeling of RNA is assessed that permits gene expression microarray analysis of formalin-fixed paraffin embedded tissue (i.e. FFPET) samples.
A novel method of amplification of FFPET-derived RNA enables accurate disease classification with microarrays.
Specimen part, Treatment
View SamplesHuman embryonic stem cells (hESCs) replicate by the process of self-renewal, whilst maintaining their pluripotency. Understanding the pathways involved in the regulation of this self-renewal process will assist in developing fully-defined conditions for the proliferation of hESCS required for therapeutic applications. We previously demonstrated a role for Sphingosine-1-phosphate (S1P) in the survival and proliferation of hESCs. The present study investigates further key signalling pathways and the downstream targets of S1P.
Sphingosine-1-phosphate mediates transcriptional regulation of key targets associated with survival, proliferation, and pluripotency in human embryonic stem cells.
No sample metadata fields
View SamplesSoybean (Glycine max) seeds are an important source of seed storage compounds, including protein, oil, and sugar used for food, feed, chemical, and biofuel production. We assessed detailed temporal transcriptional and metabolic changes in developing soybean embryos to gain a systems biology view of developmental and metabolic changes and to identify potential targets for metabolic engineering. Two major developmental and metabolic transitions were captured enabling identification of potential metabolic engineering targets specific to seed filling and to desiccation. The first transition involved a switch between different types of metabolism in dividing and elongating cells. The second transition involved the onset of maturation and desiccation tolerance during seed filling and a switch from photoheterotrophic to heterotrophic metabolism. Clustering analyses of metabolite and transcript data revealed clusters of functionally related metabolites and transcripts active in these different developmental and metabolic programs. The gene clusters provide a resource to generate predictions about the associations and interactions of unknown regulators with their targets based on guilt-by-association relationships. The inferred regulators also represent potential targets for future metabolic engineering of relevant pathways and steps in central carbon and nitrogen metabolism in soybean embryos and drought and desiccation tolerance in plants. Overall design: Total mRNA profiles of 10 time course samples of Soybean developing embryos with three replicates per sample were generated by deep sequencing, using Illumina HiSeq 2000
Transcriptome-wide functional characterization reveals novel relationships among differentially expressed transcripts in developing soybean embryos.
Age, Specimen part, Cell line, Subject
View SamplesMicroarray analysis has been applied to the study of ALS in order to investigate gene expression in whole spinal cord homogenates of SOD1 G93A mice and human ALS cases, although the massive presence of glial cells and inflammatory factors has made it difficult to define which gene expression changes were motor neuron specific. Recently, laser capture microdissection (LCM), combined with microarray analysis, has allowed the identification of motor neuron specific changes in gene expression in human ALS cases.
Microarray analysis of the cellular pathways involved in the adaptation to and progression of motor neuron injury in the SOD1 G93A mouse model of familial ALS.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Binding loci of RelA-containing nuclear factor-kappaB dimers in promoter regions of PHM1-31 myometrial smooth muscle cells.
Specimen part
View SamplesA study to define the binding loci of RelA-containing NF-kappaB dimers and subsequent correlation with gene expression in a human myometrial smooth muscle cell line after exposure to TNF.
Binding loci of RelA-containing nuclear factor-kappaB dimers in promoter regions of PHM1-31 myometrial smooth muscle cells.
Specimen part
View SamplesN6-methyladenosine (m6A) is the most abundant internal modification of eukaryotic mRNA. This modification has previously been shown to alter the export kinetics for mRNAs though the molecular details surrounding this phenomenon remain poorly understood. Here we show that the m6A complex (WTAP, KIAA1429, METTL3/14) drives recruitment of the TREX mRNA export complex onto m6A modified mRNAs and this process is essential for the efficient export of certain mRNAs. Depletion of the core m6A complex leads to loss of TREX from mRNAs which undergo the m6A modification. We show that TREX stimulates recruitment of the m6A reader protein YTHDC1 to the mRNP and the m6A complex influences the interaction of TREX with YTHDC1. We suggest that m6A acts as a surrogate for other TREX recruitment mechanisms such as splicing and 5' capping, in long internal and final exons which may otherwise be devoid of this essential complex for mRNA export. Overall design: mRNA profiles of control and Virilizer/WTAP RNAi samples in cytoplasmic and nuclear cell fractions generated by mRNA-seq in triplicate using HiSeq 2500
The m<sup>6</sup>A-methylase complex recruits TREX and regulates mRNA export.
Cell line, Subject
View SamplesOesophageal exposure to duodenogastroesophageal refluxate is implicated in the development of Barretts Metaplasia, with increased risk of progression to oesophageal adenocarcinoma. The literature proposes that reflux exposure activates NF-kB, driving the aberrant expression of intestine-specific caudal-related homeobox genes. However, early events in the pathogenesis of Barretts Metaplasia from a normal epithelium are poorly understood. To investigate this, our study subjected a 3D model of the normal human oesophageal mucosa to repeated, pulsatile exposure to specific bile components and examined changes in gene expression. Initial 2D experiments with a range of bile salts observed that taurochenodeoxycholate (TCDC) impacted upon NF-kB activation without causing cell death. Informed by this, the 3D human oesophageal model was repeatedly exposed to TCDC in the presence and absence of acid, and the epithelial cells underwent gene expression profiling. We identified ~300 differentially expressed genes following each treatment, with a large and significant overlap between treatments. Enrichment analysis (Broad GSEA, DAVID and Metacore, GeneGo Inc) identified multiple gene sets related to cell signalling, inflammation, proliferation, differentiation and cell adhesion. Specifically NF-kB activation, Wnt signalling, cell adhesion and targets for the transcription factors PTF1A and HNF4 were highlighted. CDX1/2 transcription factors are believed to play a role in BM development; however, in this study their targets were not enriched, suggesting that CDX1/2 activation may not be the one of the initial events for BM formation. Our findings highlight new areas for investigation in the earliest stages of BM pathogenesis of oesophageal diseases and new potential therapeutic targets.
Pulsatile exposure to simulated reflux leads to changes in gene expression in a 3D model of oesophageal mucosa.
No sample metadata fields
View SamplesWe examined the transcriptional effect of preventing cardiac contraction in zebrafish embryos which can be deprived of circulation without experiencing hypoxia since the fish obtain sufficient oxygen via diffusion. Morpholino antisense knockdown of cardiac troponin T2 (tnnt2) prevented cardiac contraction without affecting vascular development. We concluded that absence of hemodynamic force induces endothelial CXCR4a up-regulation and promotes recovery of blood flow.
Microarray profiling reveals CXCR4a is downregulated by blood flow in vivo and mediates collateral formation in zebrafish embryos.
Time
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