Abstract

The thymus provides an environment for the differentiation and selection of T cells, which is orchestrated by multiple supporting cell types. We applied single-cell RNA -sequencing to create a cell census of the human thymus, which unveils the diversity and coordinated development of thymic cell populations. Combining the transcriptomes with T cell receptor (TCR) repertoire profiles at single cell resolution, we construct T cell differentiation trajectory, which is accompanied by transcription factor network and TCR recombination kinetics. In addition, we identify a novel subset of agonist-selected CD8 αα+T cells which is located in the periphery of medulla and recruits XCR1 +DCs. Finally, we identify the bias in TCR recombination and selection, which could be attributed to the genomic position and MHC restriction. Especially, bias in TCR α repertoire suggests later commitment to CD8 +T cells compared to other lineage. Taken together, our findings provides comprehensive understanding on T cell development in human thymus.