CD4+ T cell help is critical for optimal CD8+ T cell expansion after priming in many experimental systems. However, a role for CD4+ T cells in regulating the initial steps of CD8+ T cell effector differentiation is not well established. Here we demonstrate that absence of CD4+ T cells at the time of replication-incompetent adenovirus vector immunization of C57BL/6 mice led to immediate CD8+ T cell dysfunction characteristic of exhaustion at the first detectable timepoints as well as impaired expansion of antigen-specific CD8+ T cells. The absence of CD4+ T cell help resulted in antigen-specific CD8+ T cells that had reduced ex vivo cytotoxicity and decreased capacity to produce IFN- and TNF-. CD8+ T cells primed in the absence of CD4+ T cells expressed elevated levels of the inhibitory receptors PD-1, LAG-3, and Tim-3, and these cells exhibited transcriptomic exhaustion profiles by gene set enrichment analysis. This dysfunctional state was imprinted within 3 days of immunization and could not be reversed by provision of CD4+ T cell help after priming. Partial rescue of unhelped CD8+ T cell expansion and effector differentiation could be achieved by PD-1 pathway blockade or recombinant IL-2 administration.
Immediate Dysfunction of Vaccine-Elicited CD8+ T Cells Primed in the Absence of CD4+ T Cells.
Specimen part, Time
View SamplesCD4 T cells promote innate and adaptive immune responses, but how vaccine-elicited CD4 T cells contribute to immune protection remains unclear.
Vaccine-elicited CD4 T cells induce immunopathology after chronic LCMV infection.
Specimen part, Time
View SamplesWe have developed a method to generate muscle stem cells from pluripotent stem cells via teratoma formation. The goal of this study is to compare the transcriptome of a7+ VCAM+ myogenic cells derived from pluripotent stem cells versus satellite cells Overall design: RNA from a7+ VCAM+ myogenic cells derived from teratoma, transplanted muscles, E14.5 mouse embryos, and hindlimbs of 8-week-old mice. In 3 biological replicates
Skeletal Muscle Stem Cells from PSC-Derived Teratomas Have Functional Regenerative Capacity.
Cell line, Subject
View SamplesHere we studied the effects of anticonvulsant drug exposure in a human embryonic stem cell (hESC) based neuro- developmental toxicity test (hESTn). During neural differentiation the cells were exposed, for either 1 or 7 days, to non-cytotoxic concentration ranges of valproic acid (VPA) or carbamazepine (CBZ), anti-epileptic drugs known to cause neurodevelopmental toxicity.
Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay.
Time
View SamplesThe ubiquitously expressed RNA-binding protein Hu Antigen R (HuR) or ELAVL1 is implicated in a variety of biological processes as well as being linked with a number of diseases, including cancer. Despite a great deal of prior investigation into HuR, there is still much to learn about its function. We take an important step in this direction by conducting iCLIP (CrossLinking and ImmunoPreciptation) and RNA Sequencing experiments followed by an extensive computational analysis to determine the characteristics of the HuR binding site and impact on the transcriptome. We reveal that HuR targets predominantly uracil-rich single-stranded stretches of varying size, with a strong conservation of structure and sequence composition. Despite the fact that HuR sites are observed in intronic regions, our data does not support a role for HuR in regulating splicing. HuR sites in 3'UTRs overlap extensively with predicted miRNA target sites suggesting interplay between the functions of HuR and miRNAs. Network analysis showed that identified targets containing HuR binding sites in the 3' UTR are highly interconnected.
Genomic analyses of the RNA-binding protein Hu antigen R (HuR) identify a complex network of target genes and novel characteristics of its binding sites.
No sample metadata fields
View SamplesZebrafish embryos have been proposed as an attractive alternative model system for hepatotoxicity testing.
A transcriptomics-based hepatotoxicity comparison between the zebrafish embryo and established human and rodent in vitro and in vivo models using cyclosporine A, amiodarone and acetaminophen.
Compound
View SamplesIn acute promyelocytic leukemia (APL), differentiation therapy with all-trans retinoic acid (ATRA)
Chemokine induction by all-trans retinoic acid and arsenic trioxide in acute promyelocytic leukemia: triggering the differentiation syndrome.
Specimen part
View SamplesWT J1 and 3B3L cells (in which Dnmt3B and Dnm3L are constitutively expressed from an exogenous construct) were cultured under both serum/LIF and 2i/LIF conditions. 3B3L cells do not show ground state-associated hypomethylation phenotype. This experiment sought to analyse the gene expression changes between the two conditions. Overall design: Three biological replicates per condition J1 serum, J1 2i, 3B3-3l serum, 3B3-3l 2i.
DNA Methylation Directs Polycomb-Dependent 3D Genome Re-organization in Naive Pluripotency.
Specimen part, Cell line, Subject
View SamplesBackground: Marketing products with added-value characteristics is a current trend in livestock production systems. Regarding meat, selection for intramuscular fat and muscular fatty acid composition is a way to improve the palatability and juiciness of meat while assuring a healthy fat content. This represents selecting animal with a different muscular metabolic profile with respect to the extended selection of lean animals. Results: The present study has analysed the muscular gene expression profiles of 68 commercial Duroc pigs belonging to two groups with extreme phenotypes for traits strongly related with lipid deposition and composition. This has allowed us to compare the physiological and metabolic implications of selecting for each of these extreme groups. Rather than upregulation of a single pathway, the main differences lied on the transcriptional levels of genes related with lipogenesis and lipolysis, revealing the existence of a cycle where triacylglycerols are continuously synthesized and degraded. Most strikingly, several genes which enhanced fatty acid -oxidation and favoured insulin signalling and glucose uptake were upregulated in the fattest animals, indicating that the events leading to peripheral insulin resistance in humans with increased levels of intramuscular fat and obesity do not take place in these pigs. Moreover, neither was detected the well-characterised low-grade inflammatory state observed in overweighed humans. Conclusion: As a whole, our data suggest that selection for increasing intramuscular fat content in pigs would lead to a shift but not a disruption of the metabolic homeostasis of muscle cells. Future studies on the post-translational changes affecting protein activity or expression as well as information about protein location within the cell would be needed to fully understand how lipid deposition affects muscle physiology in pigs.
Muscle transcriptomic profiles in pigs with divergent phenotypes for fatness traits.
Age, Specimen part
View SamplesAcute myeloid leukemia (AML) continues to have the lowest survival rates of all leukemias. Therefore, new therapeutic strategies are urgently needed to improve clinical outcomes for AML patients. Here, we report a novel role for Wilms’ tumor 1-associated protein (WTAP) in pathogenesis of AML. We have performed RNA-Seq in K562 cells with knockdown of WTAP to ascertain which genes it regulates. Overall design: We have 2 replicates of total RNA for K562 cells and 2 replicates with WTAP knocked down
WTAP is a novel oncogenic protein in acute myeloid leukemia.
Subject
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