Similar Datasets
Project description:Memory T cells provide rapid and long-term protection against infection and tumors. The memory CD8+ T cell repertoire contains phenotypically and transcriptionally heterogeneous subsets with specialized functions and recirculation patterns. While these T cell populations have been well characterized in terms of differentiation potential and function, the epigenetic changes underlying memory T cell fate determination and tissue-residency remain largely unexplored. Here, we examined the single-cell chromatin landscape of CD8+ T cells over the course of acute viral infection. We reveal an early bifurcation of memory precursors displaying distinct chromatin accessibility and define epigenetic trajectories that lead to a circulating (TCIRC) or tissue-resident memory T (TRM) cell fate. While TRM cells displayed a conserved epigenetic signature across organs, we demonstrate that these cells exhibit tissue-specific signatures and identify transcription factors that regulate TRM cell populations in a site-specific manner. Moreover, we demonstrate that TRM cells and exhausted T (TEX) cells are distinct epigenetic lineages that are distinguishable early in their differentiation. Together, these findings show that TRM cell development is accompanied by dynamic alterations in chromatin accessibility that direct a unique transcriptional program resulting in a tissue-adapted and functionally distinct T cell state.
2022-04-02 | GSE199799 | GEO
Project description:Multiome datasets of CD8+ T cells in LCMV and HSV infections
2023-09-20 | GSE243593 | GEO
Project description:scATAC-seq datasets of CD8+ T cells in LCMV and HSV infections
2023-12-26 | GSE252041 | GEO
Project description:A unique epigenomic landscape defines CD8+ tissue-resident memory T cells
| PRJNA821507 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2019-09-11 | GSE128269 | GEO
Project description:Mammalian erythropoiesis yields a highly specialized cell type, the mature erythrocyte, evolved to meet the organismal needs of increased oxygen-carrying capacity. To better understand the regulation of erythropoiesis, we performed genome-wide studies of chromatin accessibility, DNA methylation, and transcriptomics using a recently developed strategy to obtain highly purified populations of primary human erythroid cells. The integration of gene expression, DNA methylation, and chromatin state dynamics reveals that stage-specific gene regulation during erythropoiesis is a stepwise and hierarchical process involving many cis-regulatory elements. Erythroid-specific, nonpromoter sites of chromatin accessibility are linked to erythroid cell phenotypic variation and inherited disease. Comparative analyses of stage-specific chromatin accessibility indicate that there is limited early chromatin priming of erythroid genes during hematopoiesis. The epigenome of terminally differentiating erythroid cells defines a distinct subset of highly specialized cells that are vastly dissimilar from other hematopoietic and nonhematopoietic cell types. These epigenomic and transcriptome data are powerful tools to study human erythropoiesis.
| S-EPMC6863094 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-04-18 | GSE182276 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2020-01-09 | GSE118112 | GEO
Project description:Tissue resident memory CD8 T cells (TRM) serve as potent local sentinels and contribute significantly to protective immunity against intracellular mucosal pathogens. While the molecular and transcriptional underpinnings of TRM differentiation are emerging, how TRM establishment is regulated by other leukocytes in vivo is largely unclear. Here, we observed that expression of PPAR-γ in the myeloid compartment was a negative regulator of CD8 TRM establishment following influenza virus infection. Interestingly, myeloid deficiency of PPAR-γ resulted in selective impairment of the tissue-resident alveolar macrophage (AM) compartment during primary influenza infection, suggesting that AM are likely negative regulators of CD8 TRM differentiation. Indeed, influenza-specific CD8 TRM cell numbers were increased following early, but not late ablation of AM using the CD169-DTR model. Importantly, these findings were specific to the parenchyma of infected tissue as circulating memory T cell frequencies in lung and TCM and TEM in spleen were largely unaltered following macrophage ablation. Further, the magnitude of the effector response could not explain these observations. These data indicate local regulation of pulmonary TRM differentiation is alveolar macrophage dependent. These, findings could aid in vaccine design aimed at increasing TRM density to enhance protective immunity, or deflating their numbers in conditions where they cause overt or veiled chronic pathologies.
| S-EPMC6797929 | biostudies-literature
Project description:Human skin harbors two major T cell compartments of equal size that are distinguished by expression of the chemokine receptor CCR8. In vitro studies have demonstrated that CCR8 expression is regulated by TCR engagement and the skin tissue microenvironment. To extend these observations, we examined the relationship between CCR8+ and CCR8- skin T cells in vivo. Phenotypic, functional, and transcriptomic analyses revealed that CCR8+ skin T cells bear all the hallmarks of resident memory T cells, including homeostatic proliferation in response to IL-7 and IL-15, surface expression of tissue localization (CD103) and retention (CD69) markers, low levels of inhibitory receptors (programmed cell death protein 1, Tim-3, LAG-3), and a lack of senescence markers (CD57, killer cell lectin-like receptor subfamily G member 1). In contrast, CCR8- skin T cells are heterogeneous and comprise variable numbers of exhausted (programmed cell death protein 1+), senescent (CD57+, killer cell lectin-like receptor subfamily G member 1+), and effector (T-bethi, Eomeshi) T cells. Importantly, conventional and high-throughput sequencing of expressed TCR ?-chain (TRB) gene rearrangements showed that these CCR8-defined populations are clonotypically distinct, suggesting unique ontogenies in response to separate antigenic challenges and/or stimulatory conditions. Moreover, CCR8+ and CCR8- skin T cells were phenotypically stable in vitro and displayed similar levels of telomere erosion, further supporting the likelihood of a nonlinear differentiation pathway. On the basis of these results, we propose that long-lived memory T cells in human skin can be defined by the expression of CCR8.
| S-EPMC5818732 | biostudies-literature