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

Lookup NU author(s): Dr Rachel Botting, Dr Cecilia Dominguez Conde, Dr Dorin-Mirel Popescu, Emily StephensonORCiD, Dr Simone Webb, Dan Maunder, Dr David Crossland, Andrew Fuller, Dr Andrew Filby, Dr Gary ReynoldsORCiD, David Dixon, Dr Steven LisgoORCiD, Professor Deborah HendersonORCiD, Dr Roser Vento-Tormo, Professor Muzlifah Haniffa

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This is the authors' accepted manuscript of an article that has been published in its final definitive form by American Assocaition for the Advancement of Science (AAAS), 2020.

For re-use rights please refer to the publisher's terms and conditions.


Abstract

Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.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.


Publication metadata

Author(s): Park J-E, Botting RA, Dominguez 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

Publication type: Article

Publication status: Published

Journal: Science

Year: 2020

Volume: 367

Issue: 6480

Print publication date: 21/02/2020

Online publication date: 21/02/2020

Acceptance date: 16/01/2020

Date deposited: 12/03/2020

ISSN (print): 0036-8075

ISSN (electronic): 1095-9203

Publisher: American Assocaition for the Advancement of Science (AAAS)

URL: https://doi.org/10.1126/science.aay3224

DOI: 10.1126/science.aay3224

PubMed id: 32079746


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Funding

Funder referenceFunder name
203828/Z/16/A
646794
203828/Z/16/Z
Cambridge Biomedical Research Centre
BOF18-GOA-024
CZF2019-002445
EMBO Long-Term Fellowship
EU MRG-Grammar awards
GOSH BRC
Lister Insititute for Preventive Medicine and NIHR and Newcastle-Biomedical Research Centre
ERC-Stg 639429
G053816N
M362; M362-F1
UCL Therapeutic Acceletation Support Fund
WT107931/Z/15/Z
WT211276/Z/18/Z
WT MRC Cambridge Stem Cell Institute
WT206194

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