Authors: Elo Madissoon, Amanda J. Oliver, Vitalii Kleshchevnikov, Anna Wilbrey-Clark, Krzysztof Polanski, Nathan Richoz, Ana Ribeiro Orsi, Lira Mamanova, Liam Bolt, Rasa Elmentaite, J. Patrick Pett, Ni Huang, Chuan Xu, Peng He, Monika Dabrowska, Sophie Pritchard, Liz Tuck, Elena Prigmore, Shani Perera, Andrew Knights, Agnes Oszlanczi, Adam Hunter, Sara F. Vieira, Minal Patel, Rik G. H. Lindeboom, Lia S. Campos, Kazuhiko Matsuo, Takashi Nakayama, Masahiro Yoshida, Kaylee B. Worlock, Marko Z. Nikolić, Nikitas Georgakopoulos, Krishnaa T. Mahbubani, Kourosh Saeb-Parsy, Omer Ali Bayraktar, Menna R. Clatworthy, Oliver Stegle, Natsuhiko Kumasaka, Sarah A. Teichmann, Kerstin B. Meyer
Published: 2022-12-21
DOI: 10.1038/s41588-022-01243-4
Source: Full article
AbstractSingle-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 atlungcellatlas.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.