Two olive oils only differing in the presence of maslinic acid were prepared. Using DNA microarrays, hepatic gene expression was analysed in apoE-deficient mice with a C57BL/6J genetic background
Apolipoprotein E determines the hepatic transcriptional profile of dietary maslinic acid in mice.
No sample metadata fields
View SamplesAdaptive immune responses to infection result in the formation of memory T cells that respond more rapidly and robustly to reinfections, providing the basis of the immunological memory targeted by vaccines. Underlying the enhanced responsiveness of memory cells is their ability to rapidly up-regulate the transcription of key effector genes at a higher level compared to nave cells (termed transcriptional memory). While transcriptionally permissive histone modifications are known to provide chromatin structures that facilitate transcriptional memory, the molecular mechanisms that underpin this process still remain elusive. Here we investigate the transcriptional response of the Jurkat T cell line to stimulation with PMA and Ionomycin and determine if this response differs in cells that have seen stimuli previously.
Nuclear PKC-θ facilitates rapid transcriptional responses in human memory CD4+ T cells through p65 and H2B phosphorylation.
Cell line, Treatment
View SamplesRNA-seq was performed on eosinophils isolated from colons of naive C57/BL6 mice. Overall design: 2 samples of naive colonic eosinophils
Reuse of public, genome-wide, murine eosinophil expression data for hypotheses development.
Specimen part, Cell line, Subject
View SamplesThere is an increasing interest on the role of Alternative splicing (AS) in different pathologies. The Affymetrix Human Transcriptome Array (HTA 2.0) can be used to explore AS very efficiently. However, the interpretation software provided by its vendor (TAC 3.0) does not fully exploit its potential and can only be applied to case-control studies. EventPointer is an R package to identify Alternative Splicing events using HTA 2.0 arrays. It can be applied to complex experimental designs. The software provides a list of the detected events indicating the type of event (cassette, alternative 3, etc.), their statistical significance, and affected protein domains affected. The false positive rate is very low (the first detected false positive was ranked in the 149th position). EventPointer is publicly available at GitHub.
EventPointer: an effective identification of alternative splicing events using junction arrays.
Cell line
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 SamplesRecognition and removal of apoptotic cells by professional phagocytes, including dendritic cells and macrophages, preserve self-tolerance and prevent chronic inflammation and autoimmune pathologies. However the diverse array of phagocytes residing within different tissues combined with the necessarily prompt nature of apoptotic cell clearance has made it difficult to study this process in situ. Thus, the full spectrum of functions executed by tissue resident phagocytes in response to homeostatic apoptosis remains unclear.
Different tissue phagocytes sample apoptotic cells to direct distinct homeostasis programs.
Sex, Specimen part
View SamplesWe here addressed the question whether the unique capacity of mesenchymal stromal/stem cells (MSCs) to re-establish tissue homeostasis depends on their potential to sense pathogen associated molecular pattern (PAMP) and, in consequence, mount an adaptive response in the interest of tissue repair. After injection of MSCs which had been primed with the bacterial wall component LPS into murine wounds, an unexpected acceleration of healing occurred, clearly exceeding that of non-primed MSCs. This correlates with a fundamental reprogramming of the transcriptome in LPS treated MSCs as deduced from RNA-seq analysis and its validation. A network of genes mediating the adaptive response through the TLR-4 pathway responsible for neutrophil activation (GCP- 2, ENA-78, IL-1ß IL-8) and MSC protection (SOX6) profoundly contributes to enhanced wound healing. In fact, silencing of either TRL-4, or IRAK3, a downstream effector of TRL-4, or SOX6 suppressed wound healing most likely due to suppression of neutrophil extracellular trap formation and suppression of the enhanced microbicidal release of reactive oxygen species (ROS), key features of neutrophil activation. This previously unreported results uncover SOX6 which protects MSCs at the wound site from enhanced oxidative stress. This unprecedented findings hold substantial promise to refine current MSC-based therapies for difficult-to-treat wounds. Overall design: Transcriptome profiling of MSCs
TLR4-dependent shaping of the wound site by MSCs accelerates wound healing.
Treatment, Subject
View SamplesActivation of inflammatory pathways in human IBD. Leukocyte recruitment pathways including those for eosiniphils are activated in the affected colon in IBD. However, the functional implications of this are not known. We hypothesized that pro-inflammatory eotaxin (CCL11) dependent networks would be up regulated in the colon of pediatric patients with Ulcerative Colitis (UC), and that these would regulate eosinophil recruitment to the gut. These experiments tested differential colon gene expression relative to these pathways in healthy and UC samples. Colon biopsy samples were obtained from UC patients at diagnosis, and healthy controls. The global pattern of gene expression was determined using GeneSpring software, and biological networks were identified using Ingenuity software. Data suggested that a leukocyte recruitment network which includeds CCL11 is up regulated in pediatric UC at diagnosis. The degree of up regulation of these genes compared to healthy controls was remarkably conserved within the UC patient group, suggesting common mechanisms of mucosal inflammation.
Intestinal macrophage/epithelial cell-derived CCL11/eotaxin-1 mediates eosinophil recruitment and function in pediatric ulcerative colitis.
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
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