An epigenetic and transcriptomic signature of immune tolerance in human monocytes by multi-omic integration
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ABSTRACT:
PROVIDER: PRJNA672960 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12818400.fastq.gz | Fastqsanger.gz | |||
| SRR12818401.fastq.gz | Fastqsanger.gz | |||
| SRR12818402.fastq.gz | Fastqsanger.gz | |||
| SRR12818403.fastq.gz | Fastqsanger.gz | |||
| SRR12818332.fastq.gz | Fastqsanger.gz |
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Project description:This SuperSeries is composed of the SubSeries listed below.
2021-08-05 | GSE160331 | GEO
Project description:The molecular basis of TNF tolerance is poorly understood. In this experiment, primary human monocytes were used to examine TNF refractoriness. We detect absolute tolerance as selective, dose-dependently affecting a small group of powerful effector molecules; induction tolerance represented a more general phenomenon.
2014-02-11 | GSE45371 | GEO
Project description:The molecular basis of TNF tolerance is poorly understood. In this experiment, primary human monocytes were used to examine TNF refractoriness. We detect absolute tolerance as selective, dose-dependently affecting a small group of powerful effector molecules; induction tolerance represented a more general phenomenon. Primary human monocytes were incubated for 48 h with Medium or different TNF-doses and subsequently short-term stimulated for two hours with TNF. Total RNA was prepared and analysed by use of Agilent microarrays. 6 different conditions were analyzed in total, corresponding to cells that were: 1) medium incubated (M+M), 2) medium incubated and short time TNF (400 U/ml) incubated (M+T), 3) low dose TNF (40 U/ml) preincubated (40+M), 4) low dose TNF preincubated and short time TNF incubated (40+T), 5) high dose TNF (400 U/ml) preincubated (400+M), 6) high dose TNF preincubated and short time TNF incubated (400+T). 3 biological replicates (corresponding to three different healthy donors) were analyzed regarding high-dose tolerance conditions (preincubation with 400 U TNF/ml), one of which was analyzed in duplicates (including cell culture, RNA preparation and a dye-swap microarray approach). 2 biological replicates (corresponding to two different healthy donors) were analyzed under low-dose tolerance conditions (preincubation with 40 U/ml). The different human donors were numbered and indicated in brackets (d1-d5).
2014-02-11 | E-GEOD-45371 | biostudies-arrayexpress
Project description:Uncovering the mesendoderm gene regulatory network through multi-omic data integration
| PRJNA678876 | ENA
Project description:BackgroundThe plasticity of monocytes enables them to exert multiple roles during an immune response, including promoting immune tolerance. How monocytes alter their functions to convey immune tolerance in the context of lower respiratory tract infections in humans is not well understood. Here, we sought to identify epigenetic and transcriptomic features of cytokine production capacity in circulating monocytes during community-acquired pneumonia (CAP).MethodsCirculating CD14+ monocytes were obtained from the blood of CAP patients included in a longitudinal, observational cohort study, on hospitalization (acute stage, n=75), and from the same patients after a 1-month follow-up (recovery stage, n=56). Age and sex-matched non-infectious participants were included as controls (n=41). Ex vivo cytokine production after lipopolysaccharide (LPS) exposure was assessed by multiplex assay. Transcriptomes of circulating monocytes were generated by RNA-sequencing, and DNA methylation levels in the same monocytes were measured by reduced representation bisulfite sequencing. Data were integrated by fitting projection-to-latent-structure models, and signatures derived by partial least squares discrimination.ResultsMonocytes captured during the acute stage exhibited impaired TNF, IL-1β, IL-6, and IL-10 production after ex vivo stimulation with LPS, relative to controls. IL-6 production was not resolved in recovery monocytes. Multivariate analysis of RNA-sequencing data identified 2938 significantly altered RNA transcripts in acute-stage monocytes (fold expression ≤-1.5 or ≥1.5; adjusted p ≤ 0.01), relative to controls. Comparing DNA methylation levels in circulating monocytes of CAP patients to controls revealed minimal differences, specifically in DNAse hypersensitive sites (HS) of acute-stage monocytes. Data integration identified a cholesterol biosynthesis gene signature and DNAse HS axis of IL-1β and IL-10 production (R2 =0.51).ConclusionsCirculating monocytes obtained from CAP patients during the acute stage exhibited impaired cytokine production capacities, indicative of reprogramming to a state of immune tolerance, which was not fully resolved after 1 month. Our split-sample study showed that 51% of the immune tolerance phenotype can be explained, at least in part, by coordinated shifts in cholesterol biosynthesis gene expression and DNAse HS methylation levels. A multi-scale model identified an epigenetic and transcriptomic signature of immune tolerance in monocytes, with implications for future interventions in immunosuppression.Trial registrationNCT number NCT02928367.
| S-EPMC8365568 | biostudies-literature
Project description:Exposure of human monocytes to lipopolysaccharide (LPS) or other pathogen-associated molecular pattern (PAMPs) induces a temporary insensitivity to subsequent LPS challenges, a cellular state called endotoxin tolerance (ET). The tolerant state of monocytes is accompanied by cell surface and other glycoprotein expression changes induced by the activation of Toll-like receptors (TLRs). In this study, we aimed to characterize the cellular state of human monocytes stimulated with Gram-positive Staphylococcus aureus and TLR2 ligands. We analyzed gene expression changes induced by S. aureus after 2 and 24 hours by amplicon sequencing (RNA-AmpliSeq) and compared the pro-inflammatory response after 2 hours of stimulation to the to the response in re-stimulation experiments after the first stimulus. In parallel, glycoprotein expression changes in human monocytes after 24 hours of S. aureus stimulation were analyzed by proteomics and compared to stimulation experiments with TLR2 ligands Malp-2 and Pam3Cys and TLR4 ligand LPS. The results demonstrate that monocytes stimulated with S. aureus and TLR ligands entered the tolerant cell state after activation. Compared to TLR agonist mediated activation and tolerization of monocytes, glycoprotein expression changes induced by S. aureus stimulation revealed significant differences in receptor expression profiles. We report a glycoprotein expression profile characteristic for PAMP and S. aureus tolerized human monocytes. Finally, we analyzed peripheral blood monocytes of patients with S. aureus bloodstream infection for inflammatory responses in vitro and for their glycoprotein expression profiles. RNA-AmpliSeq data from patient-derived monocytes demonstrated that the cells were pro-inflammatory responsive to S. aureus stimulation and expressed higher level of CD44 mRNA, while other markers of the tolerant cell state were not detected.
2023-05-10 | PXD036036 | Pride
Project description:Disease tolerance is an important alternative strategy for rapidly acquired immunity to malaria. We show that tolerance is induced by a single malaria episode - in the absence of parasite clearance. Inflammatory spleen monocytes from C57Bl6/J mice respond with interferon-stimulated inflammation to acute first Plasmodium chabaudi infection and are destined to differentiate into inflammatory macrophages. This dramatic transcriptional response is tolerised during persisting chronic infection (with parasite densities up to 1000 parasites per µl), since the fitness costs of maintaining an emergency inflammatory response for several months would not be compatible with survival. However, spleen monocytes from chronically infected mice are not in a permanent refractory state, since their inflammatory response is identical to monocytes from uninfected mice when removed from the spleen and stimulated with LPS in vitro. Using a newly developed reinfection model to closely match parasitaemia between first and second P. chabaudi infection, we further uncover that memory of first malaria infection (30 days after drug treatment of chronic infection) dramatically changes the transcriptional response of inflammatory spleen monocytes to second infection. They now minimise inflammation and instead promote stress and tissue tolerance. This unique functional profile is not underpinned by alterations in the epigenetic landscape of inflammatory monocytes before their release from the bone marrow (link to GEO ChIPseq) - tolerance is therefore imprinted within the spleen. Hosts thus acquire long-lasting mechanisms that control inflammation (reducing collateral tissue damage) and learn to actively promote stress tolerance (protecting tissues against toxic products and processes) after one malaria episode.
2020-11-26 | GSE150047 | GEO
Project description:Omics data integration suggests a potential idiopathic Parkinson’s disease signature
| PRJNA853627 | ENA
Project description:Background: Grape cultivars and wines are distinguishable by their color, flavor and aroma profiles. Omic analyses (transcripts, proteins and metabolites) are powerful tools for assessing biochemical differences in biological systems. Results: Berry skins of red- (Cabernet Sauvignon, Merlot, Pinot Noir) and white-skinned (Chardonnay, Semillon) wine grapes were harvested near optimum maturity from the same experimental vineyard and Ë?Brix-to-titratable acidity ratio. Identical sample aliquots were analyzed for transcripts by grapevine whole-genome oligonucleotide microarray and RNA-seq technologies, proteins by nano-liquid chromatography-mass spectroscopy, and metabolites by gas chromatography-mass spectroscopy and liquid chromatography-mass spectroscopy. Principal components analysis of each of five Omic technologies showed similar results across cultivars in all Omic datasets. Comparison of the processed data of genes mapped in RNA-seq and microarray data revealed a strong Pearson's correlation (0.80). The exclusion of probesets associated with genes with potential for cross-hybridization on the microarray improved the correlation to 0.93. The overall concordance of protein with transcript data was low with a Pearson's correlation of 0.27 and 0.24 for the RNA-seq and microarray data, respectively. Integration of metabolite with protein and transcript data produced an expected model of phenylpropanoid biosynthesis, which distinguished red from white grapes, yet provided detail of individual cultivar differences. Conclusions: The five Omic technologies were consistent in distinguishing cultivar variation. There was high concordance between transcriptomic technologies, but generally protein abundance did not correlate well with transcript abundance. The integration of multiple high-throughput Omic datasets revealed complex biochemical variation amongst five cultivars of an ancient and economically important crop species. Vitis vinifera L. cv. Cabernet Sauvignon, Chardonnay, Merlot, Pinot Noir, Semillon berries were harvested from Nevada Agricultural Experiment Station Valley Road Vineyard, Reno, NV, USA. Whole-genome microarray analysis was used to assess the transcriptomic response of berry skins at harvest, approximately 24 °Brix (2011 vintage). Vines were grown under water deficit and well-watered conditions. At least two clusters harvested from non-adjacent vines were used for each of five experimental replicates.
2015-11-12 | E-GEOD-72421 | biostudies-arrayexpress
Project description:Single-cell multi-omic integration compares and contrasts features of brain cell identity
| PRJNA523430 | ENA