During meiosis in yeast, global splicing efficiency increases. The mechanism for this is relief of competition for the splicing machinery by repression of intron-containing ribosomal protein genes (RPGs). Repression of RPGs with rapamycin also increases splicing efficiency in vegetative cells. Reducing levels of an RPG-dedicated transcription factor globally improves splicing and suppresses the temperature-sensitive growth defect of a spliceosome mutation. These results indicate that the spliceosome is limiting and pre-mRNAs compete with each other. Under these conditions, splicing efficiency of a given pre-mRNA therefore depends on both its concentration and affinity for the limiting splicing factor(s) as well as those of the competing pre-mRNAs. We propose that trans-competition control of splicing helps repress meiotic gene expression in vegetative cells, and promotes efficient meiosis. Competition between RNAs for a limiting factor may be a general condition important for function of a variety of post-transcriptional control mechanisms. Overall design: Splicing and gene expression profiles of 1) wild type yeast cells treated with rapamycin (2 biological replicates) relative to untreated cells and 2) prp4-1 pGAL-IFH1 (down-regulated expression of IFH1 transcription factor(specific for ribosomal protein genes)) relative to prp4-1 yeast.
Competition between pre-mRNAs for the splicing machinery drives global regulation of splicing.
Treatment, Subject
View SamplesHsp90 is critical for regulation of the phenotype and functional activity of human T lymphocytes and natural killer (NK) cells.
Heat shock protein 90 is critical for regulation of phenotype and functional activity of human T lymphocytes and NK cells.
Specimen part, Treatment
View SamplesPyrethroids are neurotoxicants that disrupt nervous system function by interacting with a variety of membrane bound ion channels on neuronal plasma membranes. This study is designed to investigate the transcriptional events downstream of pyrethroid-induced disruption of nervous system excitability. Adult, male Long-Evans rats were orally dosed in vivo with a single dose of either permethrin (1, 10, or 100 mg/kg) or deltamethrin (0.3, 1, 3 mg/kg) at levels that produce only modest behaviroal effects in the whole animal (Wolansky et al. 2006). Transcriptional profiles were obtained from frontal cerebrocortical tissue 6 hours after acute exposure. The primary goals were 1) to identify dose-responsive biomarkers of effect for pyrethroids and 2) identify sensitive intracellular signaling or metabolic pathways sensitive to pyrethroid compounds.
Transcriptional response of rat frontal cortex following acute in vivo exposure to the pyrethroid insecticides permethrin and deltamethrin.
Sex, Specimen part
View SamplesMultiple myeloma is a fatal hematological malignancy. In order to develop effective therapeutic approaches, it is critical to understand the pathogenesis of myeloma. The Radl 5T model of multiple myeloma is a clinically relevant murine model where myeloma spontaneously occurs in aged, in-bred C57BlKalwRij mice and can be propagated by intravenous inoculation of 5T myeloma cells into mice of the same strain. Importantly inoculation of 5T myeloma cells into C57Bl6 mice does not result in myeloma, demonstrating that the bone marrow (BM) microenvironment of the C57BlKalwRij strain provides a unique and permissive milieu for myeloma development. We hypothesized that cells of the BM microenvironment may provide essential stimuli for the development of multiple myeloma in vivo. We aim to determine the differences in expression within the bone marrow of C57Bl/KalwRij mice.
Host-derived adiponectin is tumor-suppressive and a novel therapeutic target for multiple myeloma and the associated bone disease.
No sample metadata fields
View SamplesGene Expression profiling of the Arabidopsis thaliana MAP Kinase Kinases 1 (mkk1), MAP Kinase Kinases 2 (mkk2) knockout mutants and the double mutant mkk1/mkk2 before and 24 hours after treatment with the salicylic acid analog BTH, was measured by hybridisation to an Affymetrix ATH1 GeneChip.
Arabidopsis mitogen-activated protein kinase kinases MKK1 and MKK2 have overlapping functions in defense signaling mediated by MEKK1, MPK4, and MKS1.
No sample metadata fields
View SamplesRoom temperature whole blood mRNA stabilization procedures, such as the PAX gene system, are critical for the application of transcriptional analysis to population-based clinical studies. Global transcriptome analysis of whole blood RNA using microarrays has proven to be challenging due to the high abundance of globin transcripts that constitute 70% of whole blood mRNA in the blood. This is a particular problem in patients with sickle-cell disease, secondary to the high abundance of globin-expressing nucleated red blood cells and reticulocytes in the circulation . In order to more accurately measure the steady state whole blood transcriptome in sickle-cell patients, we evaluated the efficacy of reducing globin transcripts in PAXgene stabilized RNA samples for genome-wide transcriptome analyses using oligonucleotide arrays. We demonstrate here by both microarrays and Q-PCR that the globin mRNA depletion method resulted in 55-65 fold reduction in globin transcripts in whole blood collected from healthy volunteers and sickle-cell disease patients. This led to an improvement in microarray data quality with increased detection rate of expressed genes and improved overlap with the expression signatures of isolated peripheral blood mononuclear (PBMC) preparations. The differentially modulated genes from the globin depleted samples had a higher correlation coefficient to the 112 genes identified to be significantly altered in our previous study on sickle-cell disease using PBMC preparations. Additionally, the analysis of differences between the whole blood transcriptome and PBMC transcriptome reveals important erythrocyte genes that participate in sickle-cell pathogenesis and compensation. The combination of globin mRNA reduction after whole-blood RNA stabilization represents a robust clinical research methodology for the discovery of biomarkers for hematologic diseases and in multicenter clinical trials investigating a wide range of nonhematologic disorders where fractionation of cell types is impracticable.
Characterization of whole blood gene expression profiles as a sequel to globin mRNA reduction in patients with sickle cell disease.
Specimen part, Subject
View SamplesReprogram-Seq leverages organ-specific cell atlas data with single-cell perturbation and computational analysis to predict, evaluate, and optimize TF combinations that reprogram a cell type of interest. Overall design: Focusing on the cardiac system, we performed Reprogram-Seq on P0 mouse heart cells to generate a reference transcriptomic map. Based on the reference map, we selected TF candidates and tests 1000s of TF cocktails for direct lineage conversion by scRNA-Seq.
Rational Reprogramming of Cellular States by Combinatorial Perturbation.
Specimen part, Subject
View SamplesReprogram-Seq leverages organ-specific cell atlas data with single-cell perturbation and computational analysis to predict, evaluate, and optimize TF combinations that reprogram a cell type of interest. Overall design: Focusing on the cardiac system, we performed Reprogram-Seq on P0 mouse heart cells to generate a reference transcriptomic map. Based on the reference map, we selected TF candidates and tests 1000s of TF cocktails for direct lineage conversion by scRNA-Seq.
Rational Reprogramming of Cellular States by Combinatorial Perturbation.
Specimen part, Subject
View SamplesReprogram-Seq leverages organ-specific cell atlas data with single-cell perturbation and computational analysis to predict, evaluate, and optimize TF combinations that reprogram a cell type of interest. Overall design: Focusing on the cardiac system, we performed Reprogram-Seq on P0 mouse heart cells to generate a reference transcriptomic map. Based on the reference map, we selected TF candidates and tests 1000s of TF cocktails for direct lineage conversion by scRNA-Seq. This series includes uninfected, non-transformed MEFs.
Rational Reprogramming of Cellular States by Combinatorial Perturbation.
Specimen part, Subject
View SamplesTo study effects of IFNalpha treatment on monocyte-derived macrophages which may influence susceptibility or resistance to HIV.
Interleukin-27 inhibition of HIV-1 involves an intermediate induction of type I interferon.
Specimen part
View Samples