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Madissoon, Elo; Oliver, Amanda J; Kleshchevnikov, Vitalii; Wilbrey-Clark, Anna; Polanski, Krzysztof; Richoz, Nathan; Ribeiro Orsi, Ana; Mamanova, Lira; Bolt, Liam; Elmentaite, Rasa; Pett, J Patrick; Huang, Ni; Xu, Chuan; He, Peng; Dabrowska, Monika; Pritchard, Sophie; Tuck, Liz; Prigmore, Elena; Perera, Shani; Knights, Andrew; Oszlanczi, Agnes; Hunter, Adam; Vieira, Sara F; Patel, Minal; Lindeboom, Rik G H; Campos, Lia S; Matsuo, Kazuhiko; Nakayama, Takashi; Yoshida, Masahiro; Worlock, Kaylee B; Nikolić, Marko Z; Georgakopoulos, Nikitas; Mahbubani, Krishnaa T; Saeb-Parsy, Kourosh; Bayraktar, Omer Ali; Clatworthy, Menna R; Stegle, Oliver; Kumasaka, Natsuhiko; Teichmann, Sarah A; Meyer, Kerstin B
Nature genetics, 01/2023, Volume: 55, Issue: 1Journal Article
Single-cell transcriptomics has allowed unprecedented resolution of cell types/states in the human lung, but their spatial context is less well defined. To (re)define tissue architecture of lung and airways, we profiled five proximal-to-distal locations of healthy human lungs in depth using multi-omic single cell/nuclei and spatial transcriptomics (queryable at lungcellatlas.org ). Using computational data integration and analysis, we extend beyond the suspension cell paradigm and discover macro and micro-anatomical tissue compartments including previously unannotated cell types in the epithelial, vascular, stromal and nerve bundle micro-environments. We identify and implicate peribronchial fibroblasts in lung disease. Importantly, we discover and validate a survival niche for IgA plasma cells in the airway submucosal glands (SMG). We show that gland epithelial cells recruit B cells and IgA plasma cells, and promote longevity and antibody secretion locally through expression of CCL28, APRIL and IL-6. This new 'gland-associated immune niche' has implications for respiratory health.
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