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

Accepted version
Peer-reviewed

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Type

Article

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Authors

Park, Jong-Eun 
Botting, Rachel A 
Domínguez Conde, Cecilia 
Popescu, Dorin-Mirel 
Lavaert, Marieke 

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.

Description

Keywords

Atlases as Topic, CD8-Positive T-Lymphocytes, Cell Differentiation, Dendritic Cells, Fibroblasts, Humans, RNA-Seq, Receptors, Antigen, T-Cell, Single-Cell Analysis, Thymus Gland

Journal Title

Science

Conference Name

Journal ISSN

0036-8075
1095-9203

Volume Title

367

Publisher

American Association for the Advancement of Science (AAAS)

Rights

All rights reserved
Sponsorship
Wellcome Trust (203828/Z/16/Z)
Medical Research Council (MC_PC_12009)
Medical Research Council (MR/S035842/1)
Medical Research Council (MC_PC_17230)
Wellcome Trust (221052/E/20/Z)