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

ABSTRACT: 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 thymu​​s. 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), T_reg(diff), and T_reg

SUBMITTER: Heimli M 

PROVIDER: S-EPMC9895842 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature