Ontology highlight
ABSTRACT:
PROVIDER: PRJNA995237 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25295700_1.fastq.gz | Fastqsanger.gz | |||
| SRR25295700_2.fastq.gz | Fastqsanger.gz | |||
| SRR25295701_1.fastq.gz | Fastqsanger.gz | |||
| SRR25295701_2.fastq.gz | Fastqsanger.gz | |||
| SRR25295702_1.fastq.gz | Fastqsanger.gz |
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Project description:It is unclear to what extent T helper cells with a different phenotype (chemokine receptor and cytokine production profile) are generated in response to pathogen challenge or vaccination, and whether such heterogeneity can arise among the progeny of a single precursor. We combined cellular methods to isolate antigen specific T cells from different T helper memory subsets of human donors, and next generation sequencing of their TCR. This approach revealed a high level of heterogeneity in the phenotype of human T cells responding to different pathogens/vaccines also at a clonal level, as we could characterize cells bearing an identical T cell receptor with divergent effector properties. NGS-based analysis of T cell receptor repertoire of T helper memory cells identical gross specificity (i.e. responding to a given pathogen or vaccine antigen) belonging to different heper subsets (Th1, Th2, Th17)
2015-01-13 | E-GEOD-64852 | biostudies-arrayexpress
Project description:Kilian2024 - Immune cell dynamics in Cue-Induced Extended Human Colitis Model
Single-cell technologies such as scRNA-seq and flow cytometry provide critical insights into immune cell behavior in inflammatory bowel disease (IBD). However, integrating these datasets into computational models for dynamic analysis remains challenging. Here, Kilian et al., (2024) developed a deterministic ODE-based model that incorporates these technologies to study immune cell population changes in murine colitis. The model parameters were optimized to fit experimental data, ensuring an accurate representation of immune cell behavior over time. It was then validated by comparing simulations with experimental data using Pearson’s correlation and further tested on independent datasets to confirm its robustness. Additionally, the model was applied to clinical bulk RNA-seq data from human IBD patients, providing valuable insights into immune system dynamics and potential therapeutic strategies.
Figure 4c, obtained from the simulation of human colitis model is highlighted here.
This model is described in the article:
Kilian, C., Ulrich, H., Zouboulis, V.A. et al. Longitudinal single-cell data informs deterministic modelling of inflammatory bowel disease. npj Syst Biol Appl 10, 69 (2024). https://doi.org/10.1038/s41540-024-00395-9
Abstract:
Single-cell-based methods such as flow cytometry or single-cell mRNA sequencing (scRNA-seq) allow deep molecular and cellular profiling of immunological processes. Despite their high throughput, however, these measurements represent only a snapshot in time. Here, we explore how longitudinal single-cell-based datasets can be used for deterministic ordinary differential equation (ODE)-based modelling to mechanistically describe immune dynamics. We derived longitudinal changes in cell numbers of colonic cell types during inflammatory bowel disease (IBD) from flow cytometry and scRNA-seq data of murine colitis using ODE-based models. Our mathematical model generalised well across different protocols and experimental techniques, and we hypothesised that the estimated model parameters reflect biological processes. We validated this prediction of cellular turnover rates with KI-67 staining and with gene expression information from the scRNA-seq data not used for model fitting. Finally, we tested the translational relevance of the mathematical model by deconvolution of longitudinal bulk mRNA-sequencing data from a cohort of human IBD patients treated with olamkicept. We found that neutrophil depletion may contribute to IBD patients entering remission. The predictive power of IBD deterministic modelling highlights its potential to advance our understanding of immune dynamics in health and disease.
This model was curated during the Hackathon hosted by BioMed X GmbH in 2024.
2025-03-07 | MODEL2502180001 | BioModels
Project description:Naïve CD4 T cells differentiate into functionally diverse subsets of T helper (Th) cells. Gene expression profiling has the capacity to pinpoint factors that regulate subset differentiation and function, however obtaining transcriptional profiles of pure populations has been challenging. We performed single cell RNA-Sequencing (scRNA-Seq) of T helper cells from lymph node, lung and airways in a mouse model of asthma. scRNA-Seq resolved transcriptional profiles of naïve CD4 T, Th1, Th2, Treg cells and various activated states including a population responding to type I interferons. A trajectory for Th2 cell differentiation was delineated over time, with Th2 cells acquiring follicular T helper cell characteristics in the lung-draining lymph node before undergoing further modifications in the lung. A feature of airway Th2 cells was their enrichment for genes associated with lipid metabolism and experiments with blockers of key metabolic pathways supported roles for glucose and lipid metabolism in Th2 cell differentiation.
2019-06-20 | GSE131937 | GEO
Project description:Naïve CD4 T cells differentiate into functionally diverse subsets of T helper (Th) cells. Gene expression profiling has the capacity to pinpoint factors that regulate subset differentiation and function, however obtaining transcriptional profiles of pure populations has been challenging. We performed single cell RNA-Sequencing (scRNA-Seq) of T helper cells from lymph node, lung and airways in a mouse model of asthma. scRNA-Seq resolved transcriptional profiles of naïve CD4 T, Th1, Th2, Treg cells and various activated states including a population responding to type I interferons. A trajectory for Th2 cell differentiation was delineated over time, with Th2 cells acquiring follicular T helper cell characteristics in the lung-draining lymph node before undergoing further modifications in the lung. A feature of airway Th2 cells was their enrichment for genes associated with lipid metabolism and experiments with blockers of key metabolic pathways supported roles for glucose and lipid metabolism in Th2 cell differentiation.
2019-06-20 | GSE131935 | GEO
Project description:Licensing Delineates Helper and Effector NK Cell Subsets During Viral Infection
| PRJNA294518 | ENA
Project description:The contribution of CD4+ T cells to protective or pathogenic immune responses to SARS-CoV-2 infection remains unknown. Here, we present a large-scale single-cell transcriptomic analysis of viral antigen-reactive CD4+ T cells from 40 COVID-19 patients. In hospitalized patients compared to non-hospitalized patients, we found increased proportions of cytotoxic follicular helper (TFH) cells and cytotoxic T helper cells (CD4-CTLs) responding to SARS-CoV-2, and reduced proportion of SARS-CoV-2-reactive regulatory T cells (TREG). Importantly, in hospitalized COVID-19 patients, a strong cytotoxic TFH response was observed early in the illness which correlated negatively with antibody levels to SARS-CoV-2 spike protein. Polyfunctional T helper (TH)1 and TH17 cell subsets were underrepresented in the repertoire of SARS-CoV-2-reactive CD4+ T cells compared to influenza-reactive CD4+ T cells. Together, our analyses provide so far unprecedented insights into the gene expression patterns of SARS-CoV-2-reactive CD4+ T cells in distinct disease severities.
2020-10-06 | GSE152522 | GEO
Project description:We correlated comprehensive T cell phenotyping data from peripheral blood to the corresponding genotype of different disease-associated and T cell related SNPs. This revealed significantly increased frequencies of naive CD4+ T cells (CD4+ TN) and T helper 17 (TH17) cells in carriers of intergenic SNP rs56258221 (BACH2/MIR4464) as compared to non-carriers. Functional experiments identified CD4+ TN from SNP-carriers to rather polarize towards pro-inflammatory subsets than into regulatory T cells (TREG). *** Due to data privacy concerns fastq files have not been uploaded ***
2024-04-22 | E-MTAB-14013 | biostudies-arrayexpress
Project description:We correlated comprehensive T cell phenotyping data from peripheral blood to the corresponding genotype of different disease-associated and T cell related SNPs. This revealed significantly increased frequencies of naive CD4+ T cells (CD4+ TN) and T helper 17 (TH17) cells in carriers of intergenic SNP rs56258221 (BACH2/MIR4464) as compared to non-carriers. Functional experiments identified CD4+ TN from SNP-carriers to rather polarize towards pro-inflammatory subsets than into regulatory T cells (TREG). *** Due to data privacy concerns fastq files have not been uploaded ***
2024-05-22 | E-MTAB-14103 | biostudies-arrayexpress
Project description:Functionally distinct CD4+ helper T (Th) cell subsets, such as Th1, Th2, Th17, and regulatory T cells (Treg), play a pivotal role in the host-defense against pathogen invasion and the pathogenesis of inflammatory disorders. In this project, DIA-MS-based proteome analysis was performed on naïve CD4+ T, Th0, Th1, Th2, Th17 and iTreg cells using Q Exactive HF-X (Thermo Fisher Scientific) to search for proteins that differ among the cell subsets.
2023-01-04 | PXD036065 | JPOST Repository
Project description:CD4+ memory T helper cells are organized in different subsets characterized by distinct functions and chemokine receptor expression patterns induced and maintained by divergent gene programs. We demonstrate here that identical chemokine receptor combinations are sufficient to separate analogous differentiated CD8+ memory T cell subsets with matching cytokine profiles. Tc2, Tc17 and Tc22 type CD8+ T cell subsets, in contrast to classical cytotoxic Tc1 and Tc17+1 cells, possess a CD4 helper type alike phenotype characterized by absent cytotoxicity and SLAMF7 expression as well their ability to express CD40L upon activation. Their highly disparate homing patterns and unique TCR repertoire associates them to distinct immune responses as compared to those cytotoxic CD8+ T cells exert their role in. The dermal T cell gene expression signature and enrichment in psoriasis patients indicates that peripheral helper type CD8+ T cells represent a circulatory variant of skin resident cells.
2020-08-25 | GSE115103 | GEO