TY - JOUR
KW - B-Lymphocytes
KW - Epithelial Cells
KW - Humans
KW - Immunoglobulin A
KW - Lung
KW - Respiratory Mucosa
AU - Elo Madissoon
AU - Amanda J. Oliver
AU - Vitalii Kleshchevnikov
AU - Anna Wilbrey-Clark
AU - Krzysztof Polanski
AU - Nathan Richoz
AU - Ana Ribeiro Orsi
AU - Lira Mamanova
AU - Liam Bolt
AU - Rasa Elmentaite
AU - J. Patrick Pett
AU - Ni Huang
AU - Chuan Xu
AU - Peng He
AU - Monika Dabrowska
AU - Sophie Pritchard
AU - Liz Tuck
AU - Elena Prigmore
AU - Shani Perera
AU - Andrew Knights
AU - Agnes Oszlanczi
AU - Adam Hunter
AU - Sara F. Vieira
AU - Minal Patel
AU - Rik G. H. Lindeboom
AU - Lia S. Campos
AU - Kazuhiko Matsuo
AU - Takashi Nakayama
AU - Masahiro Yoshida
AU - Kaylee B. Worlock
AU - Marko Z. Nikolić
AU - Nikitas Georgakopoulos
AU - Krishnaa T. Mahbubani
AU - Kourosh Saeb-Parsy
AU - Omer Ali Bayraktar
AU - Menna R. Clatworthy
AU - Oliver Stegle
AU - Natsuhiko Kumasaka
AU - Sarah A. Teichmann
AU - Kerstin B. Meyer
AB - 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.
BT - Nature Genetics
DA - 2023-01
DO - 10.1038/s41588-022-01243-4
IS - 1
LA - eng
N2 - 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.
PY - 2023
SP - 66
EP - 77
T2 - Nature Genetics
TI - A spatially resolved atlas of the human lung characterizes a gland-associated immune niche
VL - 55
SN - 1546-1718
ER -