TY - JOUR T1 - Cross-tissue immune cell analysis reveals tissue-specific adaptations and clonal architecture across the human body JF - bioRxiv DO - 10.1101/2021.04.28.441762 SP - 2021.04.28.441762 AU - Conde C Domínguez AU - T Gomes AU - LB Jarvis AU - C Xu AU - SK Howlett AU - DB Rainbow AU - O Suchanek AU - HW King AU - L Mamanova AU - K Polanski AU - N Huang AU - E Fasouli AU - KT Mahbubani AU - M Prete AU - L Campos AU - HS Mousa AU - EJ Needham AU - S Pritchard AU - T Li AU - R Elmentaite AU - J Park AU - DK Menon AU - OA Bayraktar AU - LK James AU - KB Meyer AU - MR Clatworthy AU - K Saeb-Parsy AU - JL Jones AU - SA Teichmann Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/04/28/2021.04.28.441762.abstract N2 - Despite their crucial role in health and disease, our knowledge of immune cells within human tissues, in contrast to those circulating in the blood, remains limited. Here, we surveyed the immune compartment of lymphoid and non-lymphoid tissues of six adult donors by single-cell RNA sequencing, including alpha beta T-cell receptor (αβ TCR), gamma delta (γδ) TCR and B-cell receptor (BCR) variable regions. To aid systematic cell type identification we developed CellTypist, a tool for automated and accurate cell type annotation. Using this approach combined with manual curation, we determined the tissue distribution of finely phenotyped immune cell types and cell states. This revealed tissue-specific features within cell subsets, such as a subtype of activated dendritic cells in the airways (expressing CSF2RA, GPR157, CRLF2), ITGAD-expressing γδ T cells in spleen and liver, and ITGAX+ splenic memory B cells. Single cell paired chain TCR analysis revealed cell type-specific biases in VDJ usage, and BCR analysis revealed characteristic patterns of somatic hypermutation and isotype usage in plasma and memory B cell subsets. In summary, our multi-tissue 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.Competing Interest StatementIn the past three years, S.A.T has worked as a consultant for Genentech and Roche, and is a remunerated member of the Scientific Advisory Boards of Biogen, GlaxoSmithKline and Foresite Labs. ER -