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A cell atlas of human thymic development defines T cell repertoire formation.
Park, Jong-Eun; Botting, Rachel A; Domínguez Conde, Cecilia; Popescu, Dorin-Mirel; Lavaert, Marieke; Kunz, Daniel J; Goh, Issac; Stephenson, Emily; Ragazzini, Roberta; Tuck, Elizabeth; Wilbrey-Clark, Anna; Roberts, Kenny; Kedlian, Veronika R; Ferdinand, John R; He, Xiaoling; Webb, Simone; Maunder, Daniel; Vandamme, Niels; Mahbubani, Krishnaa T; Polanski, Krzysztof; Mamanova, Lira; Bolt, Liam; Crossland, David; de Rita, Fabrizio; Fuller, Andrew; Filby, Andrew; Reynolds, Gary; Dixon, David; Saeb-Parsy, Kourosh; Lisgo, Steven; Henderson, Deborah; Vento-Tormo, Roser; Bayraktar, Omer A; Barker, Roger A; Meyer, Kerstin B; Saeys, Yvan; Bonfanti, Paola; Behjati, Sam; Clatworthy, Menna R; Taghon, Tom; Haniffa, Muzlifah; Teichmann, Sarah A.
Afiliação
  • Park JE; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
  • Botting RA; Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
  • Domínguez Conde C; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
  • Popescu DM; Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
  • Lavaert M; Faculty of Medicine and Health Sciences, Department of Diagnostic Sciences, Ghent University, 9000 Ghent, Belgium.
  • Kunz DJ; Cancer Research Institute Ghent (CRIG), Ghent University, Ghent, Belgium.
  • Goh I; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
  • Stephenson E; Theory of Condensed Matter Group, Cavendish Laboratory/Department of Physics, University of Cambridge, Cambridge CB3 0HE, UK.
  • Ragazzini R; Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, UK.
  • Tuck E; Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
  • Wilbrey-Clark A; Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
  • Roberts K; Epithelial Stem Cell Biology and Regenerative Medicine Laboratory, Francis Crick Institute, London NW1 1AT, UK.
  • Kedlian VR; Great Ormond Street Institute of Child Health, University College London, London, UK.
  • Ferdinand JR; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
  • He X; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
  • Webb S; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
  • Maunder D; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
  • Vandamme N; Molecular Immunity Unit, Department of Medicine, University of Cambridge, MRC Laboratory of Molecular Biology, Cambridge CB2 0QQ, UK.
  • Mahbubani KT; John van Geest Centre for Brain Repair, University of Cambridge, Cambridge CB2 0PY, UK.
  • Polanski K; Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
  • Mamanova L; Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
  • Bolt L; Data Mining and Modeling for Biomedicine, VIB Center for Inflammation Research, Ghent, Belgium.
  • Crossland D; Department of Applied Mathematics, Computer Science and Statistics, Ghent University, Ghent, Belgium.
  • de Rita F; Department of Surgery, University of Cambridge and NIHR Cambridge Biomedical Research Centre, Cambridge CB2 0QQ, UK.
  • Fuller A; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
  • Filby A; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
  • Reynolds G; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
  • Dixon D; Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
  • Saeb-Parsy K; Department of Adult Congenital Heart Disease and Paediatric Cardiology/Cardiothoracic Surgery, Freeman Hospital, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne NE2 4LP, UK.
  • Lisgo S; Department of Adult Congenital Heart Disease and Paediatric Cardiology/Cardiothoracic Surgery, Freeman Hospital, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne NE2 4LP, UK.
  • Henderson D; Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
  • Vento-Tormo R; Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
  • Bayraktar OA; Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
  • Barker RA; Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
  • Meyer KB; Department of Surgery, University of Cambridge and NIHR Cambridge Biomedical Research Centre, Cambridge CB2 0QQ, UK.
  • Saeys Y; Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
  • Bonfanti P; Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
  • Behjati S; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
  • Clatworthy MR; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
  • Taghon T; John van Geest Centre for Brain Repair, University of Cambridge, Cambridge CB2 0PY, UK.
  • Haniffa M; WT-MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre Cambridge Biomedical Campus, Cambridge CB2 0AW, UK.
  • Teichmann SA; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
Science ; 367(6480)2020 02 21.
Article em En | MEDLINE | ID: mdl-32079746
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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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Atlas como Assunto / Timo / Diferenciação Celular / Linfócitos T CD8-Positivos Limite: Humans Idioma: En Revista: Science Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Reino Unido
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Atlas como Assunto / Timo / Diferenciação Celular / Linfócitos T CD8-Positivos Limite: Humans Idioma: En Revista: Science Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Reino Unido