Systematic RNA-seq analysis of the early events of CD4+ T cell activation
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE34550 | GEO | 2012/08/08
SECONDARY ACCESSION(S): PRJNA151367
REPOSITORIES: GEO
Similar Datasets
Project description:RNA-seq was used to look at the transcriptome changes and the early events of T cell receptor stimulation in CD4+ T cells CD4+ T cells were stimulated with immobilised anti-CD3/CD28 antibodies for 4 hours and RNA was extracted and subjected to RNA-seq analysis.
2012-08-08 | E-GEOD-34550 | biostudies-arrayexpress
Project description:Upon antigen-specific T Cell Receptor (TCR) engagement, human CD4+ T cells proliferate and differentiate, a process associated with rapid transcriptional changes and metabolic reprogramming utilizing aerobic glycolysis together with maintenance of oxidative phosphorylation1,2. However, the role of glycolytic-reprogramming during T-cell activation remains largely unclear3,4,5. Here, we show that maintenance of cytosolic pyruvate production is an essential requirement for remodeling of the CD4+ T cell epigenome after TCR-engagement. Furthermore, we provide evidence that the local inflammatory environment sustains metabolic reprogramming of CD4+ T-cells and impacts histone modification in a pyruvate-dependent manner. Mechanistically, we demonstrate that rapid and sustained generation of cytosolic, but not mitochondrial, pyruvate is an essential step for acetyl-coA production and subsequent H3K27ac epigenome remodeling. TCR-activation was found to induce nuclear import of pyruvate dehydrogenase (PDH) and its association with both the p300 acetyltransferase and histone H3K27ac. Disrupting PDH nuclear import impacted expression of activation-induced genes. These results reveal a direct connection between CD4+ T cell metabolic reprogramming and transcriptional regulation, with the generation of cytosolic pyruvate being an essential step in T cell activation. These data support tight integration of metabolic enzymes and histone modifying enzymes, allowing metabolic reprogramming to fuel CD4+ T cell activation.
2023-10-27 | PXD018132 | Pride
Project description:Goals and objectives of this study: to identify genes preferentially induced in human CD4+CD25hi Treg cells following T-cell activation with potential role for stabililization & maintenance of the regulatory program. Keywords: T-cell receptor stimulation, gene-regulation, comparative gene expression profiling Homo sapiens CD4+CD25- and CD4+CD25hi T cells were sorted from healthy individual donors and analyzed ex vivo (non-activated) or 1 day following T-cell receptor activation using anti-CD3/IL2 and anti-CD3/-CD28/IL2 (activated), respectively.
2009-04-20 | E-GEOD-13017 | biostudies-arrayexpress
Project description:Goals and objectives of this study: to identify genes preferentially induced in human CD4+CD25hi Treg cells following T-cell activation with potential role for stabililization & maintenance of the regulatory program. Keywords: T-cell receptor stimulation, gene-regulation, comparative gene expression profiling
2009-04-20 | GSE13017 | GEO
Project description:We used microarrays to detail the global gene transcription underlying T cells activation during the first 24 hours after stimulation. CD4+CD45RA+ T cells were sorted and cultured with different stimulatory conditions (Non-stimulated, anti-CD3 and anti-CD3 plus anti-CD28) for different times (0 hours, 4 hours and 24 hours). 3 replicates for each condition were analyzed.
2013-07-03 | E-GEOD-39594 | biostudies-arrayexpress
Project description:CD4+ T cells are at the centre of the adaptive immune system and can differentiate into distinct states that maintain self-tolerance and guide specific humoral and cellular responses to infection. Perturbation of CD4+ T cell activation is associated with many human diseases, including autoimmunity, therefore characterising the transcriptional programs underlying this process is key to the development of future therapeutic interventions. To assess the gene expression on CD4+ T cells, we recruited 20 healthy volunteers from the Cambridge BioResource. Total CD4+ T cells were isolated from whole blood within 2 hours of venepuncture. To assess the transcriptional variation in response to TCR stimulation, 1 million CD4+ T cells were cultured in U-bottom 96-well plates in the presence or absence of human T activator CD3/CD28 beads. Cells were harvested at 2 , 4, 6 or 21 hours post-stimulation, or after 0, 6 or 21 hours in the absence of stimulation. Three samples from the 6 hour unstimulated timepoint were omitted from the study due to insufficient cell numbers, and a further four samples were dropped after quality control, resulting in a total of 133 samples that were included in the final analysis.
2017-02-06 | E-MTAB-4832 | biostudies-arrayexpress
Project description:We analyzed the total proteome of CD4+ T cells isolated from WT mice, either non stimulated or at 5 different time points of stimulation with anti-CD3 and anti-CD4 antibodies (30s; 120s; 300s; 600s)
2019-09-27 | PXD012826 | Pride
Project description:Systemic lupus erythematosus is a relapsing autoimmune disease that affects multiple organ systems. T cells play an important role in the pathogenesis of lupus, however, early T cell events triggering disease flares are incompletely understood. We studied DNA methylation in naïve CD4+ T cells from lupus patients to determine if epigenetic landscape change in CD4+ T cells is an early event in lupus flares.
2017-04-10 | GSE80553 | GEO
Project description:A transgenic mouse was generated using a CD2-driven transgene containing the cDNA of Ppp2ca to achieve over-expression of PP2Ac in T cells. Naïve CD4 T cells were isolated and lysed at times 0, 6, and 24 hours after stimulation with anti-CD3 and anti-CD28 Naïve CD4 T cells from wild type mice were compared with naïve CD4 T cells from PP2Ac transgenic mice
2013-08-02 | E-GEOD-49466 | biostudies-arrayexpress
Project description:Alternative splicing consists of exons that are selectively either included or excluded from the mature mRNA transcript. Previous studies have demonstrated that ~10-15% of alternatively spliced genes undergo signal-induced changes in isoform abundance in activated primary human CD4+ T cells. In the past, signal-induced alternative splicing changes in T cells have been characterized in the context of CD3 and CD28 activation. CD3 is a component of the T Cell Receptor (TCR) which is responsible for recognizing foreign peptides presented on antigen presenting cells. CD28 enhances various signaling events downstream of the TCR to boost the survival of T cells and is required for full T cell stimulation. The contribution of CD28 signaling to transcriptional changes has been well documented, but the impact on splicing has not been investigated. Here we test the hypothesis that CD28 exerts some of its functional impact through the enhancement of splicing changes in stimulated T cells. We utilized poly(A) RNA-seq and the MAJIQ alternative splicing algorithm to analyze splicing events of human CD4+ T cells stimulated with through CD3 in the presence and absence of co-stimulation with CD28. Consistent with previous studies, we identified approximately 400 and 1,000 significant splicing events induced by CD3/CD28 stimulation at 8 and 48 hours of culture, respectively. Alternative splicing changes induced by CD3 and CD3/CD28 stimuli are highly correlative, however, approximately 23% of alternative splicing changes are further enhanced with additional CD28 costimulation at 8 hours of culture. This enhancement drops to 8% of alternative splicing events by 48 hours. Therefore, we conclude that CD28 costimulation increases the magnitude of splicing during T cell activation, in a manner that is eventually compensated for over time with CD3 stimulation alone.
2020-06-13 | GSE135118 | GEO