This SuperSeries is composed of the SubSeries listed below.
Molecular pathogenesis of post-transplant acute kidney injury: assessment of whole-genome mRNA and miRNA profiles.
Specimen part
View SamplesThe selective impact of pathogen epidemics on host defenses can be strong but remains transient. By contrast, life-history shifts can durably and continuously modify the balance between costs and benefits, which arbitrates the evolution of host defenses. Their impact, however, has seldom been documented. Here, we show with a simple mathematical model that the selective advantage of the defense system is expected to decrease with decreasing life span. We further document that, in natural populations of the model plant system Arabidopsis thaliana, the expression level of defense genes correlate positively with flowering time, a proxy for the length of vegetative life span. Using a genetic strategy to partition life span-dependent and –independent defense genes, we demonstrate that this positive co-variation is not explained by the pleiotropic action of major regulatory genes controlling both defense and life span. In agreement with our model, this study reveals that natural selection has likely assembled alleles promoting lower expression of defense genes with alleles decreasing the duration of vegetative life span in natural populations of A. thaliana. This is the first study demonstrating that life history evolution has a pervasive impact on the evolution of host immunity. Overall design: Seeds of Bur-0, Col-0 and 278 Bur-0xCol-0 Recombinant Inbred Lines (RIL) obtained after 8 generations of selfing were provided by the Arabidopsis Stock Center at INRA Versailles (France). We selected the 40 RIL in the 15% and 85% quantiles of flowering time for RNA sequencing. Each RIL and the two parental lines were planted in 20 replicates in the conditions described above. At days 14 and 28, the oldest leaf was flash-frozen in liquid nitrogen. Three pools, each combining 13 RIL, were produced at each time point for early and late lines, for a total of 3 biological replicates, 2 pool types (early and late RIL) and 2 time points (14 and 28 days). For each of the two parental lines, leaves of 12 replicates were pooled for each time point.
Assortment of Flowering Time and Immunity Alleles in Natural Arabidopsis thaliana Populations Suggests Immunity and Vegetative Lifespan Strategies Coevolve.
Specimen part, Subject, Time
View SamplesThe ability to cope with infection by a parasite is one of the major challenges for any host species and is a major driver of evolution. Parasite pressure differs between habitats. It is thought to be higher in tropical regions compared to temporal ones. We infected Drosophila melanogaster from two tropical (Malaysia and Zimbabwe) and two temperate populations (the Netherlands and North Carolina) with the generalist entomopathogenic fungus Beauveria bassiana to examine if adaptation to local parasite pressures led to differences in resistance. Contrary to previous findings we observed increased survival in temperate populations. This, however, is not due to increased resistance to infection per se, but rather the consequence of a higher general vigor of the temperate populations. We also assessed transcriptional response to infection within these flies eight and 24 hours after infection. Only few genes were induced at the earlier time point, most of which are involved in detoxification. In contrast, we identified more than 4,000 genes that changed their expression state after 24 hours. This response was generally conserved over all populations with only few genes being uniquely regulated in the temperate populations. We furthermore found that the American population was transcriptionally highly diverged from all other populations concerning basal levels of gene expression. This was particularly true for stress and immune response genes, which might be the genetic basis for their elevated vigor. Overall design: mRNA profiles of whole Drosophila melanogaster adult males from an African, American, Asian and European population after infection with Beauveria bassiana. Samples include uninfected controls, 8h after infection and 24h after infection. 3 biological replicates each (2 in the case of American controls).
Survival Rate and Transcriptional Response upon Infection with the Generalist Parasite Beauveria bassiana in a World-Wide Sample of Drosophila melanogaster.
Sex, Specimen part, Subject
View SamplesPURPOSE To identify retinal genes and their relevant expression pathways affected by intravitreal injections of dexamethasone and triamcinolone acetonide in mice at clinically relevant time points for patient care.
In vivo gene expression profiling of retina postintravitreal injections of dexamethasone and triamcinolone at clinically relevant time points for patient care.
Sex, Specimen part
View SamplesPURPOSE To identify retinal pigment epithelial (RPE)/choroid genes and their relevant expression pathways affected by intravitreal injections of dexamethasone and triamcinolone acetonide in mice at clinically relevant time points for patient care. METHODS Differential gene expression of over 34,000 well-characterized mouse genes, in the RPE/choroid of 6 week old C57BL/6J mice were analyzed after intravitreal steroid injections at 1 week and 1 month post injection, using Affymetrix Mouse Genome 430 2.0 microarrays. The data were analyzed using GeneSpringGX12.5 and Ingenuity Pathway Analysis (IPA) microarray analysis software for biologically relevant changes. RESULTS Both triamcinolone and dexamethasone caused differential activation of genes involved in Circadian Rhythm Signaling pathway at both time points tested. Triamcinolone (TAA) uniquely induced significant changes in gene expression in Calcium Signaling (1 week) and Glutamate Signaling pathways (1month). In contrast, Dexamethasone (Dex) affected the GABA Receptor Signaling (1 week) and Serotonin Receptor Signaling (1month) pathways. CONCLUSIONS Understanding how intraocular steroids affect the gene expression of RPE/choroid is clinically relevant. This in vivo study has elucidated several genes and pathways that are potentially altering the circadian rhythms and several other neurotransmitter pathways in RPE/choroid cells during intravitreal steroid injections, which likely has consequences in the dysregulation of RPE function and neurodegeneration of the retina.
Comparison of In Vivo Gene Expression Profiling of RPE/Choroid following Intravitreal Injection of Dexamethasone and Triamcinolone Acetonide.
Sex, Specimen part, Treatment
View SamplesThe CREB binding protein inhibitor ICG-001 suppresses pancreatic cancer growth
The CREB-binding protein inhibitor ICG-001 suppresses pancreatic cancer growth.
Cell line, Treatment
View SamplesGroup living animals must be able to express different behavior profiles depending on their social status. This implies that the same genotype may translate into different behavioral phenotypes through socially driven differential gene expression. Here we show for the first time that what triggers the switch between status-specific neurogenomic states is not the objective structure of the social interaction but rather the subjects perception of its outcome. For this purpose we had male zebrafish fight either a real opponent or their own image on a mirror. Massive changes in the brain transcriptome were observed in real opponent fighters, which experience either a victory or a defeat. In contrast, mirror fighters, which had no information on fight outcome despite expressing aggressive behavior, failed to activate a neurogenomic response. These results indicate that, even in cognitively simple organisms such as zebrafish, neurogenomic responses underlying changes in social status rely on cognitive appraisal.
Assessment of fight outcome is needed to activate socially driven transcriptional changes in the zebrafish brain.
Specimen part
View SamplesThe Drosophila wing disc has been a fundamental model system for the discovery of key signaling pathways and for our understanding of developmental processes. However, a complete map of gene expression in this tissue is lacking. To obtain a complete gene expression atlas in the wing disc, we employed single-cell sequencing (scRNA-seq) and developed a new method for analyzing scRNA-seq data based on gene expression correlations rather than cell mappings. This enables us to discover 824 genes with spatially restricted expression patterns, and to compute expression maps for all genes in the wing disc. This approach identifies both known and new clusters of genes with similar expression patterns and functional relevance. As proof of concept, we characterize the previously unstudied gene CG5151 and show it regulates Wnt signaling. This novel method will enable the leveraging of scRNA-seq data for generating expression atlases of undifferentiated tissues during development. Overall design: Single cell transcriptome experiments from female wandering 3rd instar wing discs were generated: two samples using Drop-seq and one sample using the 10x genomics platform. Bulk polyA-RNA-seq experiment from the same tissue was conducted for comparison.
Gene expression atlas of a developing tissue by single cell expression correlation analysis.
Sex, Specimen part, Subject
View SamplesInvestigate the effect of recombinant human IL-17A on vascular smooth muscle cells cultured from human aortas.
Interleukin (IL)-1 promotes allogeneic T cell intimal infiltration and IL-17 production in a model of human artery rejection.
No sample metadata fields
View SamplesWe have derived induced porcine pluripotent stem cells (iPPSCs) from porcine fetal fibroblasts by lentiviral transduction of four human (h) reprogramming genes, hOCT4, hSOX2, hKLF4 and hc-MYC , the same combination of factors used for deriving induced pluripotent stem cell (iPSC) lines in both mouse and human. The obtained iPPSC lines resemble human embryonic stem cells (ESC) in their gross morphology and dependence on FGF2, on the other hand, the iPPSCs share characteristics like growth rate and cell surface markers with mESC . Additionally, the iPPSCs express pluripotency- associated genes similar to mouse and human iPSCs as well as ESC, along with the pig epiblast cells. Some of the iPPSC lines retained a stable karyotype and phenotype even in culture for a prolonged period of time (passage 39). The iPPSCs can be induced to differentiate along lineages representative of the three embryonic germ layers both in vitro and in vivo demonstrating the pluripotency of these cells.
Derivation of induced pluripotent stem cells from pig somatic cells.
Specimen part
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