Adjuvants are critical for the success of vaccines, and agonists for microbial pattern recognition receptors are promising new candidates. A mechanism for the immune enhancing role of adjuvants is to stimulate innate immunity. We studied the innate immune response in humans to synthetic double stranded RNA (poly ICLC), a ligand for TLR3 and MDA-5 cytosolic RNA helicase. Transcriptional analysis of blood samples from eight volunteers, after subcutaneous administration of poly ICLC showed upregulation of genes involved in multiple innate immune pathways in all subjects, including interferon and inflammasome signaling. Blocking of type I interferon receptor ex vivo significantly dampened the response to poly IC. Comparative transcriptional analysis showed that several innate pathways were similarly induced in volunteers immunized with the highly efficacious Yellow Fever Vaccine. Therefore a chemically defined microbial agonist like poly ICLC can be a reliable and authentic microbial mimic for inducing innate immunity, here for a live attenuated viral vaccine in humans.
Synthetic double-stranded RNA induces innate immune responses similar to a live viral vaccine in humans.
Time
View SamplesSeed dormancy is the inability for seeds to germinate even under favorable conditions. In the Arabidopsis Landsberg <i>erecta</i> (L<i>er</i>) ecotype, 2 weeks of dry storage, called after-ripening, is sufficient to relieve seed dormancy. Such seed is referred to as after-ripened (AR) and has a high rate of germination when imbibed. While widespread transcriptome changes have been previously observed with seed dormancy loss, this experiment was designed to characterize transcriptional changes associated with the increased seed dormancy and dormancy loss of the gibberellin (GA) hormone-insensitive <i>sleepy1-2</i> (<i>sly1-2</i>) mutant. The <i>SLY1</i> gene encodes the F-box subunit of an SCF E3 ubiquitin ligase needed for GA-triggered proteolysis of DELLA repressors of seed germination. In the <i>sly1-2</i> mutant, GA-directed DELLA proteolysis cannot occur leading to DELLA protein accumulation and increased dormancy. <i>sly1-2</i> mutant seeds are fully dormant at 2 weeks of dry storage (0% germination), but germinate well with very long after-ripening (51% germination after 19 months). <i>sly1-2</i> seed germination can also be rescued by overexpression of the GA receptor, <i>GA-INSENSITIVE DWARF1b</i> (<i>GID1b-OE</i>), which resulted in 74% germination at 2 weeks of dry storage. In this experiment, we compared seeds of wild-type L<i>er</i> at 2 weeks of dry storage (non-dormant), dormant <i>sly1-2</i> (2 weeks of dry storage; <i>sly1-2</i>(D)), long after-ripened <i>sly1-2</i> (non-dormant, 19 months of dry storage; <i>sly1-2</i>(AR)), and <i>sly1-2 GID1b-OE</i> (non-dormant, 2 weeks of dry storage). Samples were collected at two imbibition timepoints: 1) a 0h timepoint after 4 days at 4°C, and 2) a 12h timepoint after 4 days at 4°C followed by 12 hours in the light at 22°C. These timepoints were selected to capture the transcriptomes at an early and late time in Phase II of imbibition. Using this experimental design we were able to determine transcriptome differences associated with seed dormancy in the <i>sly1-2</i> mutation (L<i>er</i> wt vs <i>sly1-2</i>(D)), and changes associated with <i>sly1-2</i> dormancy loss through dry after-ripening (<i>sly1-2</i>(AR) vs <i>sly1-2</i>(D)) or through <i>GID1b</i>-overexpression (<i>sly1-2 GID1b-OE</i> vs <i>sly1-2</i>(D)). Seeds for L<i>er</i> wt, <i>sly1-2</i>(D), and <i>sly1-2 GID1b-OE</i> were grown alongside each other under the same conditions and after-ripened for 2 weeks. Seeds from <i>sly1-2</i>(AR) were grown under the same conditions in advance of the other lines to allow for the long after-ripening requirement. RNA was extracted using a phenol-chloroform-based extraction from three biological replicates per treatment.
Transcriptional mechanisms associated with seed dormancy and dormancy loss in the gibberellin-insensitive sly1-2 mutant of Arabidopsis thaliana.
Specimen part, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Regulation of epithelial-mesenchymal transition in breast cancer cells by cell contact and adhesion.
Specimen part, Cell line
View SamplesResponse of mouse mammary epithelial cells to different cell densities and treatment with MMP3
Regulation of epithelial-mesenchymal transition in breast cancer cells by cell contact and adhesion.
Specimen part, Cell line
View SamplesResponse of mammary epithelial cells to different cell densities
Regulation of epithelial-mesenchymal transition in breast cancer cells by cell contact and adhesion.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Single-cell RNA-seq reveals cell type-specific transcriptional signatures at the maternal-foetal interface during pregnancy.
Specimen part
View SamplesOur goal was to transcriptionally profile Prdm1+ cell lineages of maternal and embryonic origin in mid-gestation mouse placenta in order to study vascular mimicry and additional processes in the placenta. Overall design: Profiling of 61 single cells and 17 clusters of 2 or 3 cells chosen based on expression of Prdm1, a paternally inherited Prdm1-Venus fluorescent reporter, progenitor trophoblast marker Gjb3 and spiral artery trophoblast giant cell marker Prl7b1.
Single-cell RNA-seq reveals cell type-specific transcriptional signatures at the maternal-foetal interface during pregnancy.
Specimen part, Cell line, Subject
View SamplesExpression profiling of wild-type and Prdm1 null mouse trophoblast giant cell cultures using Illumina whole genome mouse V2 arrays.
Single-cell RNA-seq reveals cell type-specific transcriptional signatures at the maternal-foetal interface during pregnancy.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Nos3-/- iPSCs model concordant signatures of in utero cardiac pathogenesis.
Specimen part, Time
View SamplesThrough genome-wide transcriptional comparisons, this study interrogates the capacity of iPSCs to accurately model pathogenic signatures of structural cardiac defects. Herein, we studied the molecular etiology of structural cardiac defects in Nos3-/- mice via transcriptional analysis of stage-matched embryonic and iPSC-derived tissues. In vitro comparisons of differentiated embryoid bodies were calibrated to in utero benchmarks of health and disease. Integrated systems biology analysis of WT and Nos3-/- transcriptional profiles revealed 50% concordant expression patterns between in utero embryonic and ex vivo iPSC-derived tissue. In particular, up-regulation of glucose metabolism (p-value = 3.95x10-12) and down-regulation of fatty acid metabolism (p-value = 6.71x10-12) highlight a bioenergetic signature of early Nos3 deficiency during cardiogenesis that can be recapitulated in iPSC-derived tissues. The in vitro concordance of early Nos3-/- disease signatures supports the utility of iPSCs as a cell-autonomous model of structural heart defects. Moreover, this study supports the use of iPSCs as a platform to pinpoint initial stages of cardiac pathogenesis.
Nos3-/- iPSCs model concordant signatures of in utero cardiac pathogenesis.
Specimen part, Time
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