4.8 Article

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

Journal

SCIENCE
Volume 376, Issue 6594, Pages 713-+

Publisher

AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.abl5197

Keywords

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Funding

  1. Wellcome Trust [206194, 108413/A/15/D, WSSS 211276/D/18/Z, 105924/Z/14/Z, RG79413]
  2. Chan Zuckerberg Initiative Seed Network [CZIF2019-002452]
  3. NIH [HL145547, AI128949, AI06697]
  4. European Research Council [646794 ThDEFINE]
  5. NIHR Cambridge Biomedical Research Centre [BRC-1215-20014]
  6. Chan Zuckerberg Initiative
  7. European Union [675395]
  8. Wellcome Trust [105924/Z/14/Z] Funding Source: Wellcome Trust

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This study investigated immune cells in 16 human tissues using single-cell RNA sequencing and VDJ sequencing, revealing the distribution of finely phenotyped immune cell types across tissues and uncovering tissue-specific features and clonal architecture of T and B cells.
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 similar to 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.

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