Clinical symptoms of dengue virus (DENV) infection, the most prevalent arthropod-borne viral disease, range from classical mild dengue fever to severe, life-threatening dengue shock syndrome. However, most DENV infections cause few or no symptoms. Asymptomatic DENV-infected patients provide a unique opportunity to decipher the host immune responses leading to virus elimination without negative impact on an individuals health. We used an integrated approach of transcriptional profiling and immunological analysis to compare a Cambodian population of strictly asymptomatic viremic individuals with clinical dengue patients. Whereas inflammatory pathways and innate immune response pathways were similar between asymptomatic individuals and clinical dengue patients, expression of proteins related to antigen presentation and subsequent T and B cell activation pathways were differentially regulated, independent of viral load and previous DENV infection history. Feedback mechanisms controlled the immune response in asymptomatic viremic individuals, as demonstrated by increased activation of T cell apoptosis-related pathways and FcRIIB signaling associated with decreased anti-DENV specific antibody concentrations. Taken together, our data illustrate that symptom-free DENV infection in children is associated with determined by increased activation of the adaptive immune compartment and proper control mechanisms, leading to elimination of viral infection without excessive immune activation, with implications for novel vaccine development strategies
Increased adaptive immune responses and proper feedback regulation protect against clinical dengue.
Sex, Age, Specimen part, Disease, Disease stage
View SamplesPlant hormones interact with each other and regulate gene expression to control plant growth and development. To understand the complex network, accumulation of comprehensive and integrative data of gene expression and hormone concentration is important. Using microarray, global gene expression profile was analyzed to compare with plant hormone concentration in 14 parts of rice at reproductive stage.
UniVIO: a multiple omics database with hormonome and transcriptome data from rice.
No sample metadata fields
View SamplesThe epiblast (foremost embryonic ectoderm) generates all three germ layers and therefore has crucial roles in the formation of all mammalian body cells. Regulation of epiblast gene expression is poorly understood due to the difficulty of manipulating epiblast tissues in vivo. In the present study, using the self-organizing properties of embryonic stem cells (ESCs), we generated and characterized epiblast-like tissue in three-dimensional (3D) culture. We identified significant genome-wide expression changes in this epiblast-like tissue. Additionally, we identified the significance of the Fgf/Erk and ectoderm formation pathways, using the bioinformatics resource IPA and DAVID. We first focused on Fgf5, which ranked in the top 10 among discovered genes. Toward functional analysis of Fgf5, we developed efficient methods of genome engineering (CRISPR/Cas9) and RNA interference (RNAi). Notably, we show one-step generation of an Fgf5 reporter line, null and in/del mutants. Furthermore, mutation types correlated well with CRISPR/Cas9 activity. For time- and dose-dependent depletion of Fgf5 over the course of development, we generated an ESC line harboring a drug-inducible short hairpin RNA cassette integrated by the Tol2 transposon system (pRNAi). Our methods provide a framework for a broad array of applications in the areas of mammalian genetics and molecular biology to understand development and to improve future therapeutics.
Establishment of Functional Genomics Pipeline in Mouse Epiblast-Like Tissue by Combining Transcriptomic Analysis and Gene Knockdown/Knockin/Knockout, Using RNA Interference and CRISPR/Cas9.
Specimen part
View SamplesThe unfolded protein response (UPR) is a cellular defense mechanism against glucose deprivation, a cell condition that occurs in solid tumors.
Chemical genomics identifies the unfolded protein response as a target for selective cancer cell killing during glucose deprivation.
No sample metadata fields
View SamplesNitrogen (N) is a key nutrient that is often the limiting factor in plant growth. However, the molecular mechanisms underlying transcriptional regulation of N-starvation-responses remain largely unknown.
A NIGT1-centred transcriptional cascade regulates nitrate signalling and incorporates phosphorus starvation signals in Arabidopsis.
Specimen part
View SamplesGenes related to sleep and wakefulness were evaluated by RNA microarray in patients, including CKD,HD patients and control subjects.
Messenger RNA expression profile of sleep-related genes in peripheral blood cells in patients with chronic kidney disease.
Sex, Specimen part
View SamplesInduction of germline-competent pluripotent stem cells from mouse fibroblasts has been achieved by the ectopic expression of four genes (Oct3/4, Sox2, c-Myc and Klf4). If this method can be applied to humans for the generation of personalized human pluripotent stem cells, it would greatly facilitate the therapeutic application of stem cells by avoiding the problem of immune rejection by the recipient associated with allograft transplants. Here we show that the ectopic expression of the same four genes in human neonatal skin derived cells is sufficient to induce pluripotent stem cells indistinguishable from human embryonic stem cells in morphology, gene expression, DNA methylation, teratoma formation and long term self-renewal ability. Extensive analysis of colonies generated by ectopic expression of these four genes indicates the presence of considerable heterogeneity in the induced colonies. These results provide a new finding to generate human induced pluripotent stem cells from postnatal somatic tissues.
Heterogeneity of pluripotent marker gene expression in colonies generated in human iPS cell induction culture.
No sample metadata fields
View SamplesMice with MUTYH-null allele (Mutyh+/-, Mutyh-/-) were fed a high-fat/high-cholesterol (HFHC) diet or HFHC + high iron diet. The incidence of liver tumors and histological features of the liver were compared.
MUTYH is associated with hepatocarcinogenesis in a non-alcoholic steatohepatitis mouse model.
Specimen part, Disease, Treatment
View SamplesCharacterization of the underlying genetic defects in patients with a rare and peculiar phenotype is challenging. Here we have utilized whole genome expression profiling, and identified a homozygous germline mutation in the DDB2 gene in a patient with several facial tumors. The feasibility of using blood derived RNA, diminishing costs of the technology, and the limited number of samples needed provide this approach a powerful new tool that may substantially aid in such gene identification efforts.
Blood-derived gene-expression profiling in unravelling susceptibility to recessive disease.
No sample metadata fields
View SamplesDuring a binary cell fate decision, a progeny silences the gene expression program associated with the alternative fate. Helper versus cytotoxic lineage decision in the thymus has been studied as a model for gene silencing of alternative lineage genes, including Cd4. While RUNX3 is required for the initiation of Cd4 silencing, it remains unknown how silenced states of Cd4 and other helper lineage genes are maintained. We show that the histone methyltransferase G9a is necessary for heritable silencing of Cd4 and other helper lineage genes in CD8 T cells. Despite normal Cd4 downregulation during the development, G9a-deficient CD8 T cells fail to maintain silencing of helper lineage genes when they repeatedly divide under non-inflammatory conditions. However, Cd4 depression is prevented during division driven by elevated TCR signaling and an inflammatory cytokine signaling. These results reveal the requirement for G9a in silencing of helper lineage genes in CD8 T cells and also suggest that CD8 T cells employ an alternative mechanism to maintain their cellular identity during immune responses. Overall design: RNA-sequencing on CD4+CD8+ G9a KO, CD4–CD8+ G9a KO, and CD4–CD8+ G9a WT T cells after 4 weeks of proliferation in a lymphopenic environment. ChIP-sequencing on H3K9me3 IP''ed from Ehmt2+/+ and Ehmt2-/- CD8+ T cells cultured in vitro with antibodies to CD3 and CD28
Cutting Edge: The Histone Methyltransferase G9a Is Required for Silencing of Helper T Lineage-Associated Genes in Proliferating CD8 T Cells.
Specimen part, Cell line, Subject
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