한빛사 논문
Jong-Eun Park1, Rachel A. Botting2, Cecilia Domínguez Conde1, Dorin-Mirel Popescu2, Marieke Lavaert3,4, Daniel J. Kunz1,5,6, Issac Goh2, Emily Stephenson2, Roberta Ragazzini7,8, Elizabeth Tuck1, Anna Wilbrey-Clark1, Kenny Roberts1, Veronika R. Kedlian1, John R. Ferdinand9, Xiaoling He10, Simone Webb2, Daniel Maunder2, Niels Vandamme11,12, Krishnaa T. Mahbubani13, Krzysztof Polanski1, Lira Mamanova1, Liam Bolt1, David Crossland2,14, Fabrizio de Rita14, Andrew Fuller2, Andrew Filby2, Gary Reynolds2, David Dixon2, Kourosh Saeb-Parsy13, Steven Lisgo2, Deborah Henderson2, Roser Vento-Tormo1, Omer A. Bayraktar1, Roger A. Barker10,15, Kerstin B. Meyer1, Yvan Saeys11,12, Paola Bonfanti7,8,16, Sam Behjati1,17, Menna R. Clatworthy1,9,18, Tom Taghon3,4,*, Muzlifah Haniffa1,2,19,*, Sarah A. Teichmann1,5,*
1Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
2Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
3Faculty of Medicine and Health Sciences, Department of Diagnostic Sciences, Ghent University, 9000 Ghent, Belgium.
4Cancer Research Institute Ghent (CRIG), Ghent University, Ghent, Belgium.
5Theory of Condensed Matter Group, Cavendish Laboratory/Department of Physics, University of Cambridge, Cambridge CB3 0HE, UK.
6Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, UK.
7Epithelial Stem Cell Biology and Regenerative Medicine Laboratory, Francis Crick Institute, London NW1 1AT, UK.
8Great Ormond Street Institute of Child Health, University College London, London, UK.
9Molecular Immunity Unit, Department of Medicine, University of Cambridge, MRC Laboratory of Molecular Biology, Cambridge CB2 0QQ, UK.
10John van Geest Centre for Brain Repair, University of Cambridge, Cambridge CB2 0PY, UK.
11Data Mining and Modeling for Biomedicine, VIB Center for Inflammation Research, Ghent, Belgium.
12Department of Applied Mathematics, Computer Science and Statistics, Ghent University, Ghent, Belgium.
13Department of Surgery, University of Cambridge and NIHR Cambridge Biomedical Research Centre, Cambridge CB2 0QQ, UK.
14Department of Adult Congenital Heart Disease and Paediatric Cardiology/Cardiothoracic Surgery, Freeman Hospital, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne NE2 4LP, UK.
15WT-MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre Cambridge Biomedical Campus, Cambridge CB2 0AW, UK.
16Institute of Immunity and Transplantation, University College London, London, UK.
17Department of Paediatrics, University of Cambridge, Cambridge CB2 0SP, UK.
18Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK.
19Department of Dermatology and NIHR Newcastle Biomedical Research Centre, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne NE2 4LP, UK.
*Corresponding author.
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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