A cell atlas of human thymic development defines T cell repertoire formation

single cell sequencing;SNS;单细胞测序;单细胞多组学

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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

期刊 Science
时间 2020
影响因子 63.714
起止号 367(6480):eaay3224.
种属 Mouse
技术平台单细胞测序
样本类型 T cell
研究方向技术分享
细胞类型 T细胞

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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Abstract