A cell atlas of human thymic development defines T cell repertoire formation
Authors listJong-Eun Park Rachel A Botting Cecilia Domínguez Conde Dorin-Mirel Popescu Marieke Lavaert Daniel J Kunz Issac Goh Emily Stephenson Roberta Ragazzini Elizabeth Tuck Anna Wilbrey-Clark Kenny Roberts Veronika R Kedlian John R Ferdinand Xiaoling He Simone Webb Daniel Maunder Niels Vandamme Krishnaa T Mahbubani Krzysztof Polanski Lira Mamanova Liam Bolt David Crossland Fabrizio de Rita Andrew Fuller Andrew Filby Gary Reynolds David Dixon Kourosh Saeb-Parsy Steven Lisgo Deborah Henderson Roser Vento-Tormo Omer A Bayraktar Roger A Barker Kerstin B Meyer Yvan Saeys Paola Bonfanti Sam Behjati Menna R Clatworthy Tom Taghon Muzlifah Haniffa Sarah A Teichmann
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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.