A spatially resolved atlas of the human lung characterizes a gland-associated immune niche
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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.
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Spatial distribution of cells can link multi-omics signatures of specific cell types to their localization within tissue, adding a valuable parameter to atlas production.
“This combination adds a valuable parameter to atlas production as spatial distribution of cells can tie multi-omics signatures of specific cell types with their localization within the tissue153.”
From The technological landscape and applications of single-cell multi-omics (2023) · cites this paper as [153]
Spatial multi-omics data have been used to add tissue context to cell genomic annotations through integration of complementary technologies.
“Recently, spatial multi-omics data have been used to add tissue context to cell genomic annotations through integration of multiple complementary technologies.”
From The technological landscape and applications of single-cell multi-omics (2023) · cites this paper as [153]
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Research works printed but not linked: 1
- [24]Adam, M. P. et al. (eds.) Gene Reviews (University of Washington, 2008).
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The technological landscape and applications of single-cell multi-omics
Baysoy, A., Bai, Z., Satija, R., & Fan, R. (2023) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-023-00615-w · Cited by 1,037 · see citing works
- Authors
- Madissoon, E., Oliver, A. J., Kleshchevnikov, V., Wilbrey-Clark, A., Polanski, K., Richoz, N., Ribeiro Orsi, A., Mamanova, L., Bolt, L., Elmentaite, R., Pett, J. P., Huang, N., Xu, C., He, P., Dabrowska, M., Pritchard, S., Tuck, L., Prigmore, E., Perera, S., Knights, A., Oszlanczi, A., Hunter, A., Vieira, S. F., Patel, M., Lindeboom, R. G. H., Campos, L. S., Matsuo, K., Nakayama, T., Yoshida, M., Worlock, K. B., Nikolić, M. Z., Georgakopoulos, N., Mahbubani, K. T., Saeb-Parsy, K., Bayraktar, O. A., Clatworthy, M. R., Stegle, O., Kumasaka, N., Teichmann, S. A., & Meyer, K. B.
- Affiliations
- European Bioinformatics Institute (GB)
- Wellcome Sanger Institute (GB)
- MRC Laboratory of Molecular Biology (GB)
- Kindai University (JP)
- University College London Hospitals NHS Foundation Trust (GB)
- University of Cambridge (GB)
- German Cancer Research Center (DE)
- Corresponding author
- Teichmann, Sarah A.
- Meyer, Kerstin B.
- ORCID
- 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
- Pritchard, Sophie
- Tuck, Liz
- Prigmore, Elena
- Perera, Shani
- Knights, Andrew
- Vieira, Sara F.
- 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.
- Venue
- Nature Genetics
- Published
- 2022-12-21
- Volume
- 55
- Issue
- 1
- Pages
- 66-77
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- PMC
- PMC9839452
- OpenAlex
- W4312094540
- Cited by
- 219
- References
- 135
- Citations by year
- 2026: 58 · 2025: 76 · 2024: 59 · 2023: 25
- FWCI
- 13.06
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Nature Genetics (publishedVersion, cc-by)
- Research Square (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Apollo (University of Cambridge) (submittedVersion, cc-by)
- Apollo
- Funders
- Wellcome Trust (211276, 206194, WT211276/Z/18/Z)
- European Bioinformatics Institute
- Action Medical Research (GN2911)
- University College London
- European Commission (874656, HORIZON2020, 847462)
- Rosetrees Trust
- Medical Research Council (MR/W00111X/1, MR/5005579/1, MR/S005579/1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- human lung, airway submucosal glands, IgA plasma cells, spatial transcriptomics, single-cell transcriptomics, CCL28, APRIL, interleukin-6, B cell recruitment, airway epithelium, lung stroma, lung disease
- MeSH terms
- B-Lymphocytes, Epithelial Cells, Humans, Immunoglobulin A, Lung, Respiratory Mucosa
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