see Super Series Summary Overall design: We treated Drosophila S2-DRSC cells for 1, 2, 4 and 20 h with 10 µM JQ1 and compared their gene expression to DMSO-treated control cells (1 and 20 h).
The BET protein FSH functionally interacts with ASH1 to orchestrate global gene activity in Drosophila.
Cell line, Treatment, Subject
View SamplesThe Drosophila phagocytic receptor Eater is expressed specifically in phagocytic hemocytes. It contributes to host immune defense and is required for survival of bacterial infections. Eater is involved in recognition and phagocytosis of bacteria.
Phagocytosis of bacterial pathogens.
Cell line, Treatment, Time
View SamplesWe describe the viral gene expression cascade at the single-cell level, showing bifurcations and bottleneck states. Host gene expression changes are related to viral transcription. The role of cellular signaling pathways in infection is studied using trajectory analysis and the importance of the Nrf2 transcription factor studied in follow-up experiments. Overall design: Human primary fibroblasts were infected with HSV-1 and single-cell RNA-sequencing was performed at different early time points after infection.
Single-cell RNA-sequencing of herpes simplex virus 1-infected cells connects NRF2 activation to an antiviral program.
Subject
View SamplesCircular RNAs (circRNAs) in animals are an enigmatic class of RNAs with unknown function. To systematically explore circRNAs, we sequenced and computationally analyzed human, mouse and nematode RNA. We detected thousands of well-expressed, stable circRNAs, with oftentimes tissue/developmental stage specific expression. Sequence analysis suggested important regulatory functions for circRNAs. Indeed, we discovered that human circRNA CDR1as is densely bound by miRNA effector complexes and harbors 63 conserved binding sites for the ancient miRNA miR-7. Further analyses indicated that CDR1as functions to bind miR-7 in neuronal tissues. Human CDR1as expression in zebra fish impaired midbrain development similar to knocking down miR-7, suggesting that CDR1as is a miRNA antagonist with a miRNA binding capacity ten times higher than any other known transcript. Together, our data provide evidence that circRNAs form a large class of post-transcriptional regulators. Numerous circRNAs form by head-to-tail splicing of exons, indicating previously unrecognized regulatory potential of coding sequences. Overall design: 1 Sample
Circular RNAs are a large class of animal RNAs with regulatory potency.
Cell line, Subject
View SamplesIn this study we conducted transcriptomics analyses of: (i) liver samples from patients suffering from acetaminophen-induced acute liver failure (n=3) and from healthy livers (n=2) and (ii) hepatic cell systems exposed to acetaminophen, including their respective vehicle controls. The investigated in vitro systems are: HepaRG cells, HepG2 cells and a novel human skinpostnatal stem cell-derived model i.e. human skin-precursors-derived hepatocyte-like cells (hSKP-HPC).
Gene expression data from acetaminophen-induced toxicity in human hepatic <i>in vitro</i> systems and clinical liver samples.
Specimen part, Disease stage, Cell line
View SamplesHuman skin-derived precursor cells (hSKP) are a post natal stem cell population isolated from the dermis. These cells acquire hepatic characteristics upon differentiation with hepatogenic factors. Differentiated hSKP show characteristics of hepatocyte precursor cells and respond to hepatotoxic compounds in a comparable way as human hepatocyte cultures.
In vitro assessment of drug-induced liver steatosis based on human dermal stem cell-derived hepatic cells.
Sex, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Snail regulates MyoD binding-site occupancy to direct enhancer switching and differentiation-specific transcription in myogenesis.
Specimen part, Disease, Time
View SamplesIn skeletal myogenesis, the transcription factor MyoD activates distinct transcriptional programs in progenitors compared to terminally differentiated cells. Using ChIP-seq and gene expression analyses, we show that in primary myoblasts, Snail-HDAC1/2 repressive complex bind and exclude MyoD from its targets. Notably, Snail binds E-box motifs that are G/C-rich in their central dinucleotides, and such sites are almost exclusively associated with genes expressed during differentiation. By contrast, Snail does not bind the A/T-rich E-boxes associated with MyoD targets in myoblasts. Thus, Snai1-HDAC1/2 prevents MyoD occupancy on differentiation-specific regulatory elements and the change from Snail- to MyoD-binding often results in enhancer switching during differentiation. Furthermore, we show that a regulatory network involving Myogenic Regulatory Factors (MRFs), Snail/2, miR-30a and miR-206 acts as a molecular switch that controls entry into myogenic differentiation. Together, these results reveal a regulatory paradigm that directs distinct gene expression programs in progenitors versus terminally differentiated cells.
Snail regulates MyoD binding-site occupancy to direct enhancer switching and differentiation-specific transcription in myogenesis.
Specimen part, Time
View SamplesIdentifying immune correlates of protection and mechanisms of immunity accelerates and streamlines the development of vaccines. RTS,S/AS01E, the most advanced malaria vaccine, has moderate efficacy in African children. In contrast, immunization with sporozoites under antimalarial chemoprophylaxis (CPS immunization) can provide 100% sterile protection in naïve adults. We used systems biology approaches to identify correlates of vaccine-induced immunity based on transcriptomes of peripheral blood mononuclear cells from subjects immunized with RTS,S/AS01E or chemo-attenuated sporozoites stimulated with parasite antigens in vitro. Specifically, we used samples of subjects from two age cohorts and 3 African countries participating in an RTS,S/AS01E pediatric phase 3 trial and malaria-naïve subjects participating in a CPS trial. We identified both pre-immunization and post-immunization transcriptomic signatures correlating with protection. Signatures were validated in independent children and infants from the RTS,S/AS01E phase 3 trial and subjects from an independent CPS trial with high accuracies (>70%). Transcription modules revealed interferon, NF-B, TLR, and monocyte-related signatures associated with protection. Pre-immunization signatures suggest the potential for strategies to prime the immune system before vaccination towards improving vaccine immunogenicity and efficacy. Finally, signatures of protection could be useful to determine efficacy in clinical trials, accelerating vaccine candidate testing. Nevertheless, signatures should be tested more extensively across multiple cohorts and trials to demonstrate their universal predictive capacity.
Antigen-stimulated PBMC transcriptional protective signatures for malaria immunization.
Sex, Specimen part, Subject, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genome-wide analysis shows that Ldb1 controls essential hematopoietic genes/pathways in mouse early development and reveals novel players in hematopoiesis.
Specimen part
View Samples