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Multimodal human thymic profiling reveals trajectories and cellular milieu for T agonist selection

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE207206 | GEO | 2023/02/01

REPOSITORIES: GEO

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Multimodal human thymic profiling reveals trajectories and cellular milieu for T agonist selection.

Project description:To prevent autoimmunity, thymocytes expressing self-reactive T cell receptors (TCRs) are negatively selected, however, divergence into tolerogenic, agonist selected lineages represent an alternative fate. As thymocyte development, selection, and lineage choices are dependent on spatial context and cell-to-cell interactions, we have performed Cellular Indexing of Transcriptomes and Epitopes by sequencing (CITE-seq) and spatial transcriptomics on paediatric human thymus. Thymocytes expressing markers of strong TCR signalling diverged from the conventional developmental trajectory prior to CD4+ or CD8+ lineage commitment, while markers of different agonist selected T cell populations (CD8αα(I), CD8αα(II), T(agonist), Treg(diff), and Treg) exhibited variable timing of induction. Expression profiles of chemokines and co-stimulatory molecules, together with spatial localisation, supported that dendritic cells, B cells, and stromal cells contribute to agonist selection, with different subsets influencing thymocytes at specific developmental stages within distinct spatial niches. Understanding factors influencing agonist T cells is needed to benefit from their immunoregulatory effects in clinical use.

| S-EPMC9895842 | biostudies-literature

Multimodal human thymic profiling reveals trajectories and cellular milieu for T agonist selection [Spatial transcriptomics]

Project description:To prevent autoimmunity, thymocytes expressing self-reactive T cell receptors (TCRs) are negatively selected, however, divergence into tolerogenic, agonist-selected lineages represent an alternative fate. As thymocyte development, selection, and lineage choices are dependent on spatial context and cell-to-cell interactions, we have performed Cellular Indexing of Transcriptomes and Epitopes by sequencing (CITE-seq) and spatial transcriptomics on paediatric human thymus. Thymocytes expressing markers of strong TCR signalling diverged from the conventional developmental trajectory prior to CD4+ lineage commitment, while markers of different agonist cell populations (CD8αα(I), CD8αα(II), T(agonist), Treg(diff) and Treg) exhibited variable timing of induction. Expression profiles of chemokines and co-stimulatory molecules, together with spatial localization, supported that dendritic cells, B cells, and stromal cells contribute to agonist selection, with different subsets influencing thymocytes at specific developmental stages within distinct spatial niches. Understanding factors influencing agonist T cells is needed to benefit from their immunoregulatory effects in clinical use.

2023-02-01 | GSE207205 | GEO

Multimodal human thymic profiling reveals trajectories and cellular milieu for T agonist selection [CITE-seq]

Project description:To prevent autoimmunity, thymocytes expressing self-reactive T cell receptors (TCRs) are negatively selected, however, divergence into tolerogenic, agonist-selected lineages represent an alternative fate. As thymocyte development, selection, and lineage choices are dependent on spatial context and cell-to-cell interactions, we have performed Cellular Indexing of Transcriptomes and Epitopes by sequencing (CITE-seq) and spatial transcriptomics on paediatric human thymus. Thymocytes expressing markers of strong TCR signalling diverged from the conventional developmental trajectory prior to CD4+ lineage commitment, while markers of different agonist cell populations (CD8αα(I), CD8αα(II), T(agonist), Treg(diff) and Treg) exhibited variable timing of induction. Expression profiles of chemokines and co-stimulatory molecules, together with spatial localization, supported that dendritic cells, B cells, and stromal cells contribute to agonist selection, with different subsets influencing thymocytes at specific developmental stages within distinct spatial niches. Understanding factors influencing agonist T cells is needed to benefit from their immunoregulatory effects in clinical use.

2023-02-01 | GSE207204 | GEO

Multimodal human thymic profiling reveals trajectories and cellular milieu for T agonist selection

Project description:Multimodal human thymic profiling reveals trajectories and cellular milieu for T agonist selection

| PRJNA854141 | ENA

Multimodal human thymic profiling reveals trajectories and cellular milieu for T agonist selection [Spatial transcriptomics]

Project description:Multimodal human thymic profiling reveals trajectories and cellular milieu for T agonist selection [Spatial transcriptomics]

| PRJNA854149 | ENA

Multimodal human thymic profiling reveals trajectories and cellular milieu for T agonist selection [CITE-seq]

Project description:Multimodal human thymic profiling reveals trajectories and cellular milieu for T agonist selection [CITE-seq]

| PRJNA854148 | ENA

Single-cell transcriptional profiling of human thymic stroma uncovers novel cellular heterogeneity in the thymic medulla.

Project description:The thymus' key function in the immune system is to provide the necessary environment for the development of diverse and self-tolerant T lymphocytes. While recent evidence suggests that the thymic stroma is comprised of more functionally distinct subpopulations than previously appreciated, the extent of this cellular heterogeneity in the human thymus is not well understood. Here we use single-cell RNA sequencing to comprehensively profile the human thymic stroma across multiple stages of life. Mesenchyme, pericytes and endothelial cells are identified as potential key regulators of thymic epithelial cell differentiation and thymocyte migration. In-depth analyses of epithelial cells reveal the presence of ionocytes as a medullary population, while the expression of tissue-specific antigens is mapped to different subsets of epithelial cells. This work thus provides important insight on how the diversity of thymic cells is established, and how this heterogeneity contributes to the induction of immune tolerance in humans.

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Cellular milieu of the neural retina informs complement immune regulation

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-01-24 | GSE117959 | GEO

Global transcriptional profiling reveals distinct functions of thymic stromal subsets and age-related changes during thymic involution.

Project description:Age-associated thymic involution results in diminished T cell output and function in aged individuals. However, molecular mediators contributing to the decline in thymic function during early thymic involution remain largely unknown. Here, we present transcriptional profiling of purified thymic stromal subsets from mice 1, 3, and 6 months of age spanning early thymic involution. The data implicate unanticipated biological functions for a subset of thymic epithelial cells. The predominant transcriptional signature of early thymic involution is decreased expression of cell-cycle-associated genes and E2F3 transcriptional targets in thymic epithelial subsets. Also, expression of proinflammatory genes increases with age in thymic dendritic cells. Many genes previously implicated in late involution are already deregulated by 3-6 months of age. We provide these thymic stromal data sets, along with thymocyte data sets, in a readily searchable web-based platform, as a resource for investigations into thymocyte:stromal interactions and mechanisms of thymic involution.

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Multimodal profiling of lung granulomas in macaques reveals cellular correlates of tuberculosis control

Project description:We used longitudinal scRNA-seq, PET-CT, and bacterial burden assays to understand the cellular features underlying granuloma timing and burden/resolution.

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