A spatially resolved atlas of the human lung characterizes a gland-associated immune niche
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
Abstract
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.
Datasets
1. All cells and nuclei
Metadata
Celltypes
Celltypes_master_high
Celltypes_master_higher
Celltypes_master_higher_immune
Loc_true
suspension_type
donor_id
Gender
Sample
ID
Protocol_plot
assay_ontology_term_id
Study
PoolDon
DonorPool
scDonor_snBatch
disease_ontology_term_id
organism_ontology_term_id
donor_id_2
sex_ontology_term_id
self_reported_ethnicity_ontology_term_id
Age range
Smoking status
BMI range
development_stage_ontology_term_id
Location_long
Cell_fraction
tissue_ontology_term_id
cell_type_ontology_term_id
tissue_type
cell_type
assay
disease
organism
sex
tissue
self_reported_ethnicity
development_stage
Macro_alveolar17098 cells Fibro_adventitial10170 cells Endothelia_vascular_Cap_g9348 cells CD4_EM/Effector6367 cells Macro_intravascular5033 cells Endothelia_Lymphatic3885 cells Endothelia_vascular_venous_systemic3798 cells Endothelia_vascular_Cap_a3247 cells Macro_intermediate2598 cells Endothelia_vascular_arterial_pulmonary2172 cells Endothelia_vascular_venous_pulmonary2075 cells Muscle_smooth_pulmonary1789 cells Secretory_Goblet1632 cells Muscle_pericyte_pulmonary1359 cells Fibro_peribronchial1083 cells Fibro_myofibroblast870 cells Muscle_perivascular_immune_recruiting679 cells Muscle_smooth_arterial_systemic645 cells Muscle_smooth_airway505 cells Fibro_perichondrial411 cells Macro_alveolar_metallothioneins410 cells Macro_interstitial335 cells Endothelia_vascular_arterial_systemic215 cells Muscle_pericyte_systemic179 cells Schwann_nonmyelinating112 cells Fibro_immune_recruiting59 cells Schwann_Myelinating11 cells Endothelia_vascular20855 cells Macrophage_alveolar17254 cells Submucosal_Glands13373 cells Macrophage_other11069 cells Endothelia_lymphatic3885 cells HCA_A_LNG93877135593 cells HCA_A_LNG93877185463 cells HCA_A_LNG93877145251 cells HCA_A_LNG93877175215 cells HCA_A_LNG93877165055 cells HCA_A_LNG93877155036 cells WTDAtest85501274337 cells WSSS_A_LNG87579274226 cells HCA_A_LNG93877113963 cells HCA_A_LNG93877103932 cells HCA_A_LNG93877123668 cells WSSS_A_LNG87579293477 cells WTDAtest77322693425 cells WSSS_A_LNG87579283377 cells HCATisStab77322623322 cells HCA_A_LNG93877093149 cells WTDAtest77322703126 cells WTDAtest77322652874 cells WSSS_A_LNG86200632792 cells 5841STDY79914752578 cells WSSS_A_LNG86200592323 cells HCATisStab77322642304 cells WSSS_A_LNG86200622296 cells WTDAtest77322682238 cells HCATisStab77322631981 cells 5841STDY79914821973 cells WTDAtest77322671937 cells WTDAtest79850961865 cells 5841STDY79914831854 cells WTDAtest77322661789 cells 5841STDY79914791528 cells 5841STDY79914871454 cells 5841STDY79914861410 cells WSSS_A_LNG86200611358 cells 5841STDY79914781295 cells WSSS_A_LNG86200601081 cells WSSS_A_LNG86200681021 cells HCATisStab7732261826 cells WSSS_A_LNG8620064793 cells WSSS_A_LNG8620065590 cells WSSS_A_LNG8620066556 cells WSSS_A_LNG8620067304 cells A43-LNG-1-SC-45N-210941 cells A40-LNG-4-SC-45P-18981 cells A40-LNG-5-SC-45P-18288 cells A43-LNG-2-SC-45N-25997 cells HCA_A_LNG93877135593 cells HCA_A_LNG93877185463 cells A43-LNG-5-SC-45N-25323 cells HCA_A_LNG93877145251 cells HCA_A_LNG93877175215 cells HCA_A_LNG93877165055 cells HCA_A_LNG93877155036 cells A43-LNG-3-SC-45N-24743 cells WTDAtest85501274337 cells WSSS_A_LNG87579274226 cells A40-LNG-3-SC-45P-14126 cells HCA_A_LNG93877113963 cells HCA_A_LNG93877103932 cells HCA_A_LNG93877123668 cells A44-LNG-5-SC-45N-13656 cells WSSS_A_LNG87579293477 cells A26-LNG-1-SC-45N-53425 cells WSSS_A_LNG87579283377 cells HCATisStab77322623322 cells A44-LNG-5-SC-45P-13246 cells HCA_A_LNG93877093149 cells A44-LNG-1-SC-45N-12925 cells A26-LNG-2-SC-45P-52874 cells A47-LNG-3-SC-1st-12792 cells A37-LNG-1-SC-45P-12578 cells A40-LNG-3-SC-45N-12568 cells A47-LNG-1-SC-1st-12323 cells HCATisStab77322642304 cells A47-LNG-2-SC-2nd-12296 cells A26-LNG-1-SC-45P-52238 cells A40-LNG-2-SC-45N-12171 cells A44-LNG-4-SC-45N-12120 cells A40-LNG-1-SC-45N-12050 cells HCATisStab77322631981 cells A37-LNG-1-SC-45N-11973 cells WTDAtest79850961865 cells A37-LNG-2-SC-45N-11854 cells A40-LNG-1-SC-45P-11829 cells A26-LNG-2-SC-45N-51789 cells A37-LNG-5-SC-45P-11528 cells A37-LNG-5-SC-45N-11454 cells A37-LNG-4-SC-45N-21410 cells A40-LNG-2-SC-45P-11365 cells A47-LNG-2-SC-1st-11358 cells A37-LNG-4-SC-45P-21295 cells A40-LNG-4-SC-45N-11242 cells A44-LNG-2-SC-45P-11187 cells A47-LNG-1-SC-2nd-11081 cells A47-LNG-5-SC-2nd-11021 cells A44-LNG-2-SC-45N-11008 cells A37-LNG-3-SC-45N-1983 cells A44-LNG-3-SC-45N-1925 cells A44-LNG-1-SC-45P-1828 cells HCATisStab7732261826 cells A47-LNG-3-SC-2nd-1793 cells A37-LNG-4-SC-45P-1777 cells A37-LNG-4-SC-45N-1718 cells A40-LNG-5-SC-45N-1665 cells A47-LNG-4-SC-1st-1590 cells A47-LNG-4-SC-2nd-1556 cells A37-LNG-3-SC-45P-1445 cells A44-LNG-4-SC-45P-1349 cells A47-LNG-5-SC-1st-1304 cells A32-LNG-1-SC-45P-1243 cells A32-LNG-1-SC-45N-1233 cells A32-LNG-2-SC-45P-1220 cells A32-LNG-2-SC-45N-1110 cells A44-LNG-3-SC-45P-150 cells LibCD45neg_TrypLibUndigest55069 cells TrypLibUndigest10810 cells NCBITaxon:9606193108 cells HANCESTRO:0005193108 cells HsapDv:000015843777 cells HsapDv:000024127277 cells HsapDv:000012927004 cells HsapDv:000016925687 cells HsapDv:000015223094 cells HsapDv:000015320690 cells HsapDv:000016016294 cells Lower Left Lobe46091 cells Upper left lobe29983 cells Bronchi 4th divison with surrounding parenchyma18038 cells Bronchi 2-3 divison with surrounding parenchyma17425 cells Bronchi 2-3 divison without surrounding parenchyma6854 cells CD45neg and Liberase undigested55069 cells Liberase undigested5747 cells UBERON:000204846325 cells UBERON:000895346091 cells UBERON:000218542317 cells UBERON:000895229983 cells UBERON:000312628392 cells type II pneumocyte18372 cells alveolar macrophage17098 cells blood vessel endothelial cell12595 cells natural killer cell12309 cells lung macrophage10466 cells adventitial cell10170 cells fibroblast of lung7420 cells type I pneumocyte7315 cells lung secretory cell6951 cells effector CD4-positive, alpha-beta T cell6367 cells CD14-positive monocyte5932 cells vein endothelial cell5873 cells effector memory CD8-positive, alpha-beta T cell5866 cells serous secreting cell of bronchus submucosal gland5180 cells endothelial cell of lymphatic vessel3885 cells lung resident memory CD8-positive, alpha-beta T cell3877 cells naive thymus-derived CD4-positive, alpha-beta T cell3804 cells pulmonary artery endothelial cell2172 cells respiratory suprabasal cell1918 cells lung resident memory CD4-positive, alpha-beta T cell1859 cells smooth muscle cell of the pulmonary artery1789 cells plasmacytoid dendritic cell1623 cells mucosal invariant T cell1254 cells airway submucosal gland duct basal cell1184 cells bronchus fibroblast of lung1083 cells myofibroblast cell870 cells gamma-delta T cell841 cells regulatory T cell808 cells blood vessel smooth muscle cell645 cells innate lymphoid cell517 cells smooth muscle cell505 cells myoepithelial cell439 cells lung perichondrial fibroblast411 cells metallothionein-positive alveolar macrophage410 cells conventional dendritic cell395 cells lung interstitial macrophage335 cells endothelial cell of artery215 cells mesothelial cell140 cells non-myelinating Schwann cell112 cells deuterosomal cell71 cells neuroendocrine cell44 cells myelinating Schwann cell11 cells 10x 5' transcription profiling104712 cells lower lobe of left lung46091 cells upper lobe of left lung29983 cells 64-year-old human stage43777 cells seventh decade human stage27277 cells 35-year-old human stage27004 cells 75-year-old human stage25687 cells 58-year-old human stage23094 cells 59-year-old human stage20690 cells 66-year-old human stage16294 cells sixth decade human stage8479 cells 29-year-old human stage806 cells Analyze this study
Source data
https://cellxgene.cziscience.com/collections/c1241244-b22d-483d-875b-75699efb9f3c
Alias names
PRJEB52292, E-MTAB-11640, S-BIAD570, PMID36543915, PMC9839452
Cite this study
Madissoon, E., Oliver, A.J., Kleshchevnikov, V., Wilbrey-Clark, A., Polanski, K., Richoz, N., Ribeiro Orsi, A., Mamanova, L., Bolt, L., Elmentaite, R. and Pett, J.P., 2023. A spatially resolved atlas of the human lung characterizes a gland-associated immune niche. Nature Genetics, 55(1), pp.66-77. https://doi.org/10.1038/s41588-022-01243-4
