Purpose: The goals of this study are to compare transcriptome profiling (RNA-seq) in pancreatic intraepithelial neoplasm (PanIN) cells exposed to tobacco-specific nitrosamine 4-(methyl nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and to examine the upregulated pathways. Overall design: Methods: Total RNA was isolated from PanIN cells treated with tobacco specific nitrosamine 4-(methyl nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) for 5 and 50 days. Samples were processed for RNA-seq using standard methods on the Illumina HiSeq 2000 platform. Sequencing was performed in two multiplexed lanes of 100-bp single-end sequencing, which resulted in 75 million mappable reads per lane. The Illumina pipeline was used for base calling and quality filtering of sequence reads. Transcript assembly and abundance estimates of transcripts in fragments per kilobase of exon per million fragments mapped (FPKM) were performed by Cufflinks. Significant differences in total gene and transcript expression, splice site, transcription start site (TSS) and promoter usage were determined using a false discovery rate (FDR)-adjusted P-value. This study provides a framework for understanding transcriptional changes when pancreas cells exposed to tobacco specific nitrosamine.
Tobacco Carcinogen-Induced Production of GM-CSF Activates CREB to Promote Pancreatic Cancer.
Specimen part, Cell line, Subject, Time
View SamplesAdaptation of C. elegans to hypertonic environments involves the accumulation of the organic osmolyte glycerol via transcriptional upregulation of the glycerol biosynthestic enzyme gpdh-1. A number of mutants, termed osmotic stress resistant (osr) mutants, have been identified. osr mutants cause constitutive upregulation of gpdh-1 and confer extreme resistance to hypertonicity. We tested the hypothesis that osr mutants broadly activate a gene expression program normally activated by osmotic stress in wild type animals using Affymterix microarray analysis of the hypertonic stress response in wild type animals and of constituitive gene expression changes in five osr mutants.
Genetic and physiological activation of osmosensitive gene expression mimics transcriptional signatures of pathogen infection in C. elegans.
Specimen part
View SamplesThe role of infection in erythropoietic dysfunction is poorly understood. In children with P. falciparum malaria, the by-product of hemoglobin digestion in infected red cells (hemozoin) is associated with the severity of anemia which is independent of circulating levels of the inflammatory cytokine tumor necrosis alpha (TNF-alpha). To gain insight into the common and specific effects of TNF-alpha and hemozoin on erythropoiesis, we studied the gene expression profile of purified primary erythroid cultures exposed to either TNF-alpha (10ng/ml) or to hemozoin (12.5microgram/ml heme units) for 24 hours. Perturbed gene function was assessed using co-annotation of associated gene ontologies and expression of selected genes representative of the profile observed was confirmed by real time PCR (rtPCR). The changes in gene expression induced by each agent were largely distinct; many of the genes significantly modulated by TNF-alpha were not affected by hemozoin.
Distinct mechanisms of inadequate erythropoiesis induced by tumor necrosis factor alpha or malarial pigment.
Specimen part
View SamplesIn vertebrate muscle, loss of Dysferlin results in the activation of compensatory muscle gene expression, even at pre-pathological stages. We hypothesized that if C. elegans fer-1 is also expressed in muscle, then fer-1 mutant worms might also exhibit compensatory muscle gene expression.
C. elegans dysferlin homolog fer-1 is expressed in muscle, and fer-1 mutations initiate altered gene expression of muscle enriched genes.
Specimen part
View SamplesFunctional discrimination between normal centroblast and centrocyte obtained from human inflamed tonsils after cell sorting.
CXCR4 expression functionally discriminates centroblasts versus centrocytes within human germinal center B cells.
Specimen part
View SamplesTonEBP is a transcription factor that promotes cellular accumulation of organic osmolytes in the hypertonic renal medulla by stimulating expression of its target genes. Genetically modified animals with deficient TonEBP activity in the kidney suffer from severe medullary atrophy in association with cell death, demonstrating that TonEBP is essential for the survival of the renal medullary cells. Using both TonEBP knockout cells and RNA interference of TonEBP, we found that TonEBP promoted cellular adaptation to hypertonic stress. Microarray analyses revealed that genetic response to hypertonicity was dominated by TonEBP in that expression of totally different sets of genes was increased by hypertonicity in those cells with TonEBP vs. those without TonEBP activity. Out of over 100 potentially new TonEBP regulated genes, we selected 7 for further analyses and found that their expression was all dependent on TonEBP. RNA interference experiments showed that some of these genes asporin, insulin-like growth factor-binding protein 5 and 7, and an extracellular lysophosphlipase D plus Hsp70, a known TonEBP target gene, contributed to the adaptation to hypertonicity without promoting organic osmolyte accumulation. We conclude that TonEBP stimulates multiple cellular pathways for adaptation to hypertonic stress in addition to organic osmolyte accumulation.
TonEBP stimulates multiple cellular pathways for adaptation to hypertonic stress: organic osmolyte-dependent and -independent pathways.
Specimen part
View SamplesGEP on Affymetrix Genechip HTA 2.0 microarrays was performed on ex vivo cell-sorted GC-Tfh and pre-Tfh from TONS and FL
Human Lymphoid Stromal Cells Contribute to Polarization of Follicular T Cells Into IL-4 Secreting Cells.
Specimen part, Treatment
View SamplesGEP on Affymetrix U133+2.0 microarrays was performed on in vitro expanded stromal cells
Human Lymphoid Stromal Cells Contribute to Polarization of Follicular T Cells Into IL-4 Secreting Cells.
Specimen part
View SamplesGene expression profiles were assessed for vincristine-sensitive parental ovarian tumor cell line (SKOV3) and its highly vincristine-resistant derivative (SKVCR 2.0)
Genetic changes in the evolution of multidrug resistance for cultured human ovarian cancer cells.
No sample metadata fields
View SamplesThese arrays are used for various projects
DNA amplification is a ubiquitous mechanism of oncogene activation in lung and other cancers.
Sex, Age, Race
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