Park, J-E; Botting, RA; Domínguez Conde, C; Popescu, D-M; Lavaert, M; Kunz, DJ; Goh, I; ... Teichmann, SA; + view all Park, J-E; Botting, RA; Domínguez Conde, C; Popescu, D-M; Lavaert, M; Kunz, DJ; Goh, I; Stephenson, E; Ragazzini, R; Tuck, E; Wilbrey-Clark, A; Roberts, K; Kedlian, VR; Ferdinand, JR; He, X; Webb, S; Maunder, D; Vandamme, N; Mahbubani, KT; Polanski, K; Mamanova, L; Bolt, L; Crossland, D; de Rita, F; Fuller, A; Filby, A; Reynolds, G; Dixon, D; Saeb-Parsy, K; Lisgo, S; Henderson, D; Vento-Tormo, R; Bayraktar, OA; Barker, RA; Meyer, KB; Saeys, Y; Bonfanti, P; Behjati, S; Clatworthy, MR; Taghon, T; Haniffa, M; Teichmann, SA; - view fewer (2020) A cell atlas of human thymic development defines T cell repertoire formation. Science , 367 (6480) , Article eaay3224. 10.1126/science.aay3224.

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Abstract

The thymus provides a nurturing environment for the differentiation and selection of T cells, a process orchestrated by their interaction with multiple thymic cell types. We used single-cell RNA sequencing to create a cell census of the human thymus across the life span and to reconstruct T cell differentiation trajectories and T cell receptor (TCR) recombination kinetics. Using this approach, we identified and located in situ CD8αα+ T cell populations, thymic fibroblast subtypes, and activated dendritic cell states. In addition, we reveal a bias in TCR recombination and selection, which is attributed to genomic position and the kinetics of lineage commitment. Taken together, our data provide a comprehensive atlas of the human thymus across the life span with new insights into human T cell development.

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