Stepwise activation of primary human memory CD4+ T cells
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ABSTRACT:
PROVIDER: PRJNA1222425 | ENA |
REPOSITORIES: ENA
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Project description:Memory CD4+ T cells sequentially restructure their 3D genome during stepwise activation
| PRJNA1222427 | ENA
Project description:CD4+ T cells are a highly differentiated cell type that maintain enough transcriptomic plasticity to cycle between activated and memory statuses. We generated RNA-seq libraries from T-cells harvested from three independent blood donors under three separate conditions: unstimulated fresh ex vivo, IL-2 only stimulated and TCR+CD28+IL-2 stimulated, conferring increasingly stronger activation signals. .
2025-02-11 | GSE288509 | GEO
Project description:In order investigate the control of genes encoding cytoskeletal motor proteins and their interaction partners in primary T-cells, we performed whole transcriptome microarray profiling of cell activation for memory and naïve T-cells isolated from three anonymous blood donors. CD4+CD25- naïve or memory T-cells were cultured in medium alone or stimulated ex vivo and harvested for total RNA isolation and whole transcriptome microarray analysis.
2013-01-23 | E-GEOD-33272 | biostudies-arrayexpress
Project description:Obtaining a complete picture of 3D-genome organization in tissues and disease states is often blocked by limiting amounts of tissue samples such that multiple types of genome-wide analyses cannot be performed on the same sample. Here, we found that starting with a pure population of memory CD4+ T-cells (mCD4-cells) we could get reproducible Hi-C data with just 50,000 cells. This population is only ~18.75% of the whole T-cell population, but presumably its uniformity enabled high reproducibility with low cell numbers so that Hi-C, RNA-Seq and potentially other analyses could be performed with repeats from the same donor. Moreover, there was strong correspondence between data from 3 different donors, suggesting that variability between individuals observed in other reports may reflect more the dynamic variability in the status of the immune system between individuals rather than variability in genome organization between individuals for a given cell type. We further observed uniform changes between samples and blood donors occurring during activation of the memory mCD4+ T cell population. While some genome organization changes occurred concomitant with changes in gene expression, there were at least as many changes that occurred without corresponding changes in expression. Counter to the hypothesis that TADs are largely invariant structures providing a scaffold for dynamic looping contacts between enhancers and promotors, we found that there were at least as many dynamic TAD changes as loops in this highly differentiated cell type. Stimulation with IL-2 alone triggered many changes in genome organization and many of these changes were strengthened by additional TCR and CD28 co-receptor stimulation. This suggests a stepwise process whereby mCD4+ T cells undergo sequential genome organization changes induced by distinct or combined stimuli likely to "prime" or “de-prime” them for expression responses to subsequent TCR-antigen ligation or additional cytokine stimulation
2025-02-11 | GSE288510 | GEO
Project description:Human CD4 memory T cell activation time course
| PRJNA666468 | ENA
Project description:Human CD4 memory T cell activation time course
| PRJNA666467 | ENA
Project description:Memory T cells are primed for rapid responses to antigen; however, the molecular mechanisms responsible for priming remain incompletely defined. CpG methylation in promoters is an epigenetic modification, which regulates gene transcription. Using targeted bisulfite sequencing, we examined methylation of 2100 genes (56,000 CpG) mapped by deep sequencing to T cell activation in human naïve and memory CD4 T cells. 466 CpGs (132 genes) displayed differential methylation between naïve and memory cells. 21 genes exhibited both differential methylation and gene expression before activation, linking promoter DNA methylation states to gene regulation; 6 genes encode proteins closely studied in T cells while 15 genes represent novel targets for further study. 39 genes exhibited reduced methylation in memory cells coupled with increased gene expression with activation compared to naïve cells, revealing specific genes more rapidly expressed in memory compared to naïve cells and potentially regulated by DNA methylation. These findings define a DNA methylation signature unique to memory CD4 T cells and correlated with activation-induced gene expression. transcriptome of primary human naïve and memory CD4 T cells at rest and 48 hours post-activation.
2015-01-20 | E-GEOD-58684 | biostudies-arrayexpress
Project description:Memory T cells are primed for rapid responses to antigen; however, the molecular mechanisms responsible for priming remain incompletely defined. CpG methylation in promoters is an epigenetic modification, which regulates gene transcription. Using targeted bisulfite sequencing, we examined methylation of 2100 genes (56,000 CpG) mapped by deep sequencing to T cell activation in human naïve and memory CD4 T cells. 466 CpGs (132 genes) displayed differential methylation between naïve and memory cells. 21 genes exhibited both differential methylation and gene expression before activation, linking promoter DNA methylation states to gene regulation; 6 genes encode proteins closely studied in T cells while 15 genes represent novel targets for further study. 39 genes exhibited reduced methylation in memory cells coupled with increased gene expression with activation compared to naïve cells, revealing specific genes more rapidly expressed in memory compared to naïve cells and potentially regulated by DNA methylation. These findings define a DNA methylation signature unique to memory CD4 T cells and correlated with activation-induced gene expression. RNA sequencing of primary human naïve and memory CD4 T cells at rest and 48 hours post-activation.
2015-01-20 | E-GEOD-59846 | biostudies-arrayexpress
Project description:Memory T cells are primed for rapid responses to antigen; however, the molecular mechanisms responsible for priming remain incompletely defined. CpG methylation in promoters is an epigenetic modification, which regulates gene transcription. Using targeted bisulfite sequencing, we examined methylation of 2100 genes (56,000 CpG) mapped by deep sequencing to T cell activation in human naïve and memory CD4 T cells. 466 CpGs (132 genes) displayed differential methylation between naïve and memory cells. 21 genes exhibited both differential methylation and gene expression before activation, linking promoter DNA methylation states to gene regulation; 6 genes encode proteins closely studied in T cells while 15 genes represent novel targets for further study. 39 genes exhibited reduced methylation in memory cells coupled with increased gene expression with activation compared to naïve cells, revealing specific genes more rapidly expressed in memory compared to naïve cells and potentially regulated by DNA methylation. These findings define a DNA methylation signature unique to memory CD4 T cells and correlated with activation-induced gene expression. Targeted bisulfite sequencing of primary human naïve and memory CD4 T cells at rest and 48 hours post-activation.
2015-01-20 | E-GEOD-59858 | biostudies-arrayexpress
Project description:Differentiation of CD4+T-cells into effector subsets is a critical component of the adaptive immune system and an incorrect response can lead to autoimmunity or immune deficiency. Cellular differentiation including T-cell differentiation is accompanied by large-scale epigenetic remodeling, including changes in DNA methylation at key regulators of T-cell differentiation. The TET family of enzymes were recently shown to be able to catalyse methylated cytosine (5mC) into 5-hydroxymethylcytosine (5hmC) enabling a pathway of active removal of DNA methylation. Here, we characterize 5hmC, 5mC and transcriptional dynamics during human CD4+T-cell polarisation in a time series approach and relate these changes to profiles in ex-vivo CD4+memory subsets. We observed large-scale remodelling during early CD4+T-cell differentiation which was predictive of subsequent changes during late time points, these changes were also related to disease associated regions which we show can act as functional regulatory elements. This dataset was designed to assess how DNA methylation differs between in-vivo derived CD4+memory T-cell subsets. DNA methylation was assessed in relationship to gene expression levels and changes (see data series), we observed anticorrelation between promoter DNA methylation levels and gene expression. This submission contains data from DNA methylation profiling of primary human CD4+T-cell memory subsets. This is part of a series, containing transcription and DNA methylation profiling of the same samples. See related experiments E-MTAB-4685, E-MTAB-4686, E-MTAB-4687, E-MTAB-4688
2016-07-11 | E-MTAB-4689 | biostudies-arrayexpress