Cross-tissue immune cell analysis reveals tissue-specific features in humans.

Journal: Science (New York, N.Y.)
PMID: 35549406

Abstract

Despite their crucial role in health and disease, our knowledge of immune cells within human tissues remains limited. We surveyed the immune compartment of 16 tissues from 12 adult donors by single-cell RNA sequencing and VDJ sequencing generating a dataset of ~360,000 cells. To systematically resolve immune cell heterogeneity across tissues, we developed CellTypist, a machine learning tool for rapid and precise cell type annotation. Using this approach, combined with detailed curation, we determined the tissue distribution of finely phenotyped immune cell types, revealing hitherto unappreciated tissue-specific features and clonal architecture of T and B cells. Our multitissue approach lays the foundation for identifying highly resolved immune cell types by leveraging a common reference dataset, tissue-integrated expression analysis, and antigen receptor sequencing.

Authors

  • C Domínguez Conde
    Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.
  • C Xu
    Department of Biostatistics and Epidemiology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA.
  • L B Jarvis
    Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
  • D B Rainbow
    Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
  • S B Wells
    Department of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA.
  • T Gomes
    Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.
  • S K Howlett
    Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
  • O Suchanek
    Molecular Immunity Unit, Department of Medicine, University of Cambridge, Cambridge, UK.
  • K Polanski
    Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.
  • H W King
    Centre for Immunobiology, Blizard Institute, Queen Mary University of London, London, UK.
  • L Mamanova
    Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.
  • N Huang
    Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.
  • P A Szabo
    Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY, USA.
  • L Richardson
    Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.
  • L Bolt
    Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.
  • E S Fasouli
    Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.
  • K T Mahbubani
    Department of Surgery, University of Cambridge and NIHR Cambridge Biomedical Research Centre, Cambridge, UK.
  • M Prete
    Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.
  • L Tuck
    Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.
  • N Richoz
    Molecular Immunity Unit, Department of Medicine, University of Cambridge, Cambridge, UK.
  • Z K Tuong
    Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.
  • L Campos
    Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.
  • H S Mousa
    Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
  • E J Needham
    Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
  • S Pritchard
    Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.
  • T Li
    Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.
  • R Elmentaite
    Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.
  • J Park
  • E Rahmani
    Center for Computational Biology, University of California, Berkeley, Berkeley, CA, USA.
  • D Chen
    Physikalisch-Technische Bundesanstalt, Braunschweig and Berlin, Germany.
  • D K Menon
    Department of Anaesthesia, University of Cambridge, Cambridge, UK.
  • O A Bayraktar
    Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.
  • L K James
    Centre for Immunobiology, Blizard Institute, Queen Mary University of London, London, UK.
  • K B Meyer
    Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.
  • N Yosef
    Center for Computational Biology, University of California, Berkeley, Berkeley, CA, USA.
  • M R Clatworthy
    Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.
  • P A Sims
    Department of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA.
  • D L Farber
    Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY, USA.
  • K Saeb-Parsy
    Department of Surgery, University of Cambridge and NIHR Cambridge Biomedical Research Centre, Cambridge, UK.
  • J L Jones
    Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
  • S A Teichmann
    Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.

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