Regulatory T cells (Tregs) are essential for maintaining proper immune homeostasis. Extracellular signals (e.g. TCR, CD28, IL-2R) are necessary for the generation and maintenance of Tregs, but how these signals are integrated to control the gene expression patterns of Tregs is less clear. Here we show that the epigenetic regulator, Ezh2, was induced by CD28 costimulation and Ezh2 activity was elevated in Tregs as compared to conventional CD4+ T cells. Deletion of Ezh2 in mouse Tregs led to a progressive autoimmune disease because Tregs were compromised after activation, losing proper control of essential Treg lineage genes and adopting a gene expression pattern similar to Foxp3-deficient ‘Tregs.’ Lineage-tracing of Ezh2-deficient Tregs in vivo confirmed that the cells were destabilized selectively in activated Treg populations, which led to a significant loss of Tregs in non-lymphoid tissues. These studies reveal an essential role for Ezh2 in the maintenance of Treg “identity” during cellular activation and differentiation. Overall design: RNAseq of sorted populations of CD62Lhi or CD62Llo Tregs for both Ezh2-HET (Foxp3YFP-Cre/Foxp3WT;Ezh2fl/+ female mice) and Ezh2-KO (Foxp3YFP-Cre/Foxp3WT;Ezh2fl/fl female mice) were generated, in triplicate for each condition, using Illumina HiSeq 2500 single-end 50bp sequencing platform.
The chromatin-modifying enzyme Ezh2 is critical for the maintenance of regulatory T cell identity after activation.
No sample metadata fields
View SamplesAdult right ventricle from Tetralogy of Fallot patients undergoing pulmonary valve replacement vs right ventricle myocardium from unused donor hearts
Right Ventricle Has Normal Myofilament Function But Shows Perturbations in the Expression of Extracellular Matrix Genes in Patients With Tetralogy of Fallot Undergoing Pulmonary Valve Replacement.
Specimen part
View SamplesPBMC from house dust mite (HDM) sensitized atopics were cultured in the presence or absence of HDM extract for 24 hours.
Distinguishing benign from pathologic TH2 immunity in atopic children.
No sample metadata fields
View SamplesPBMC from house dust mite (HDM) sensitized atopics with or without asthma (or nonallergic controls) were cultured in the presence or absence of HDM extract for 24 hours.
Differential gene network analysis for the identification of asthma-associated therapeutic targets in allergen-specific T-helper memory responses.
Specimen part, Disease stage, Subject
View SamplesBACKGROUND: Streptococcus pneumoniae, the pneumococcus, is the main etiological agent of pneumonia. Pneumococcal infection is initiated by bacterial adherence to lung epithelial cells. The exact transcriptional changes occurring in both host and microbe during infection are unknown. Here, we developed a time-resolved infection model of human lung alveolar epithelial cells by S. pneumoniae and assess the resulting transcriptome changes in both organisms simultaneously by using dual RNA-seq. RESULTS: Functional analysis of the time-resolved dual RNA-seq data identifies several features of pneumococcal infection. For instance, we show that the glutathione-dependent reactive oxygen detoxification pathway in epithelial cells is activated by reactive oxygen species produced by S. pneumoniae. Addition of the antioxidant resveratrol during infection abates this response. At the same time, pneumococci activate the competence regulon during co-incubation with lung epithelial cells. By comparing transcriptional changes between wild-type encapsulated and mutant unencapsulated pneumococci, we demonstrate that adherent pneumococci, but not free-floating bacteria, repress innate immune responses in epithelial cells including expression of the chemokine IL-8 and the production of antimicrobial peptides. We also show that pneumococci activate several sugar transporters in response to adherence to epithelial cells and demonstrate that this activation depends on host-derived mucins. CONCLUSIONS: We provide a dual-transcriptomics overview of early pneumococcal infection in a time-resolved manner, providing new insights into host-microbe interactions. To allow easy access to the data by the community, a web-based platform was developed ( http://dualrnaseq.molgenrug.nl ). Further database exploration may expand our understanding of epithelial-pneumococcal interaction, leading to novel antimicrobial strategies. Overall design: 5 time points are analysed (0, 30, 60, 120 and 240 minutes after infection). Each time point has two biological replicates except for the 240 mpi. Furthermore, each time point has two pneumococcal strains used to infect A549 cells, encapsulated and unencapsulated pneumococci. In total there are 18 samples. cellular infection model, contains rRNA-depleted total RNA from A549 epithelial cells and D39 S. pneumoniae
Time-resolved dual RNA-seq reveals extensive rewiring of lung epithelial and pneumococcal transcriptomes during early infection.
Specimen part, Cell line, Subject
View SamplesAnalysis of expression profiles of human pDC cell line (CAL1) compared to an immature T cell line (MOLT4)
Transcription factor E2-2 is an essential and specific regulator of plasmacytoid dendritic cell development.
No sample metadata fields
View SamplesAnalysis of expression profiles of pDCs from wild type and heterozygous E2-2 mice. Results show the control by E2-2 of the expression of pDC-enriched genes.
Transcription factor E2-2 is an essential and specific regulator of plasmacytoid dendritic cell development.
No sample metadata fields
View SamplesIn this randomised placebo-controlled trial, irritable bowel syndrome (IBS) patients were treated with faecal material from a healthy donor (n=8, allogenic FMT) or with their own faecal microbiota (n=8, autologous FMT). The faecal transplant was administered by whole colonoscopy into the caecum (30 g of stool in 150 ml sterile saline). Two weeks before the FMT (baseline) as well as two and eight weeks after the FMT, the participants underwent a sigmoidoscopy, and biopsies were collected at a standardised location (20-25 cm from the anal verge at the crossing with the arteria iliaca communis) from an uncleansed sigmoid. In patients treated with allogenic FMT, predominantly immune response-related genes sets were induced, with the strongest response two weeks after FMT. In patients treated with autologous FMT, predominantly metabolism-related gene sets were affected.
Allogenic Faecal Microbiota Transfer Induces Immune-Related Gene Sets in the Colon Mucosa of Patients with Irritable Bowel Syndrome.
Age, Specimen part, Subject
View SamplesGene expression was compared for wild type yeast (BY4741) and yeast lacking Gal11/Med15 and Med3, or from a gal11-myc med3 strain. The gal11-myc allele shows a partial loss of function when combined with med3. Expression was analyzed for yeast grown in YPD as well as in CSM.
Distinct role of Mediator tail module in regulation of SAGA-dependent, TATA-containing genes in yeast.
No sample metadata fields
View SamplesIntra-islet crosstalk between islet cells is critical in orchestrating the body’s response to changes in blood glucose levels, but is incompletely understood. In this study, we used transgenic mouse lines that allowed the purification and transcriptomic characterisation of alpha, beta, and delta cells, yielding an RNA-sequencing database that can be searched for regulatory proteins which are differentially expressed between cell types. As an illustrative example, we examined the expression of g-protein coupled receptors, and found that the ghrelin receptor, Ghsr, was highly expressed in delta cells compared to alpha and beta cells. GHSR excitation elicited increases in cytosolic calcium levels in primary delta cells. In the perfused pancreas, the application of ghrelin stimulated somatostatin secretion, correlating with a decrease in insulin and glucagon release, which was sensitive to somatostatin receptor antagonism. These results show that ghrelin acts specifically on delta cells within pancreatic islets to affect blood glucose regulation. Overall design: Examination of transcriptomic profiles obtained from pancreatic alpha, beta and delta cells
Transcriptomic profiling of pancreatic alpha, beta and delta cell populations identifies delta cells as a principal target for ghrelin in mouse islets.
Specimen part, Cell line, Subject
View Samples