A cell atlas of human thymic development defines T cell repertoire formation (Mouse thymus)

Jong-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

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 CD8<ce><b1><ce><b1>+ 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.