A cellular census of human lungs identifies novel cell states in health and in asthma
Open accessAbstract
Human lungs enable efficient gas exchange and form an interface with the environment, which depends on mucosal immunity for protection against infectious agents. Tightly controlled interactions between structural and immune cells are required to maintain lung homeostasis. Here, we use single-cell transcriptomics to chart the cellular landscape of upper and lower airways and lung parenchyma in healthy lungs, and lower airways in asthmatic lungs. We report location-dependent airway epithelial cell states and a novel subset of tissue-resident memory T cells. In the lower airways of patients with asthma, mucous cell hyperplasia is shown to stem from a novel mucous ciliated cell state, as well as goblet cell hyperplasia. We report the presence of pathogenic effector type 2 helper T cells (T H 2) in asthmatic lungs and find evidence for type 2 cytokines in maintaining the altered epithelial cell states. Unbiased analysis of cell-cell interactions identifies a shift from airway structural cell communication in healthy lungs to a T H 2-dominated interactome in asthmatic lungs.
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Analyzed samples in prior human upper airway scSeq datasets did not include any olfactory sensory neurons or sustentacular cells, indicating that tissue sampling did not include the olfactory epithelium.
“However, analyzed samples in these datasets did not include any OSNs or sustentacular cells, indicating that tissue sampling in these experiments did not include the OE (41, 42).”
From Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia (2020) · cites this paper as [42]
Two data sets of the human cell atlas were used: a Drop-seq data set measured in lung tissue52 and a Smart-seq2 data set measured in pancreas tissue51.
“Two data sets of the human cell atlas were used for that, a Drop-seq data set measured in lung tissue52 and a Smart-seq2 data set measured in pancreas tissue51.”
From scPower accelerates and optimizes the design of multi-sample single cell transcriptomic studies (2021) · cites this paper as [52]
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Fischer, D. S., Dony, L., König, M., Moeed, A., Zappia, L., Heumos, L., Tritschler, S., Holmberg, O., Aliee, H., & Theis, F. J. (2021) · Genome Biology · doi:10.1186/s13059-021-02452-6 · Cited by 33 · see citing works
Self-citation
- Authors
- Vieira Braga, F. A., Kar, G., Berg, M., Carpaij, O. A., Polanski, K., Simon, L. M., Brouwer, S., Gomes, T., Hesse, L., Jiang, J., Fasouli, E. S., Efremova, M., Vento-Tormo, R., Talavera-López, C., Jonker, M. R., Affleck, K., Palit, S., Strzelecka, P. M., Firth, H. V., Mahbubani, K. T., Cvejic, A., Meyer, K. B., Saeb-Parsy, K., Luinge, M., Brandsma, C.-A., Timens, W., Angelidis, I., Strunz, M., Koppelman, G. H., van Oosterhout, A. J., Schiller, H. B., Theis, F. J., van den Berge, M., Nawijn, M. C., & Teichmann, S. A.
- Affiliations
- Wellcome Sanger Institute (GB)
- University Medical Center Groningen (NL)
- Helmholtz Munich (DE)
- GlaxoSmithKline (United Kingdom) (GB)
- Wellcome/MRC Cambridge Stem Cell Institute (GB)
- University of Cambridge (GB)
- Corresponding author
- Nawijn, Martijn C.
- Teichmann, Sarah A.
- ORCID
- Vieira Braga, Felipe A.
- Kar, Gozde
- Berg, Marijn
- Carpaij, Orestes A.
- Simon, Lukas M.
- Gomes, Tomás
- Hesse, Laura
- Fasouli, Eirini S.
- Efremova, Mirjana
- Talavera-López, Carlos
- Jonker, Marnix R.
- Strzelecka, Paulina M.
- Firth, Helen V.
- Mahbubani, Krishnaa T.
- Cvejic, Ana
- Meyer, Kerstin B.
- Saeb-Parsy, Kourosh
- Brandsma, Corry-Anke
- Timens, Wim
- Angelidis, Ilias
- Koppelman, Gerard H.
- Schiller, Herbert B.
- Theis, Fabian J.
- Nawijn, Martijn C.
- Teichmann, Sarah A.
- Venue
- Nature Medicine
- Published
- 2019-06-17
- Volume
- 25
- Issue
- 7
- Pages
- 1153-1163
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2950891712
- Cited by
- 896
- References
- 54
- Citations by year
- 2026: 74 · 2025: 107 · 2024: 122 · 2023: 125 · 2022: 156 · 2021: 164 · 2020: 127 · 2019: 20
- FWCI
- 80.09
- Type
- journal article
- Language
- en
- Open access
- Licence
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Site cant be reached (submittedVersion, other-oa)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion)
- Queen Mary Research Online (Queen Mary University of London) (submittedVersion)
- VUBIR (Vrije Universiteit Brussel) (submittedVersion)
- Apollo (University of Cambridge) (submittedVersion)
- Apollo
- Funders
- GlaxoSmithKline
- Wellcome Trust (211276/Z/18/Z)
- Universitair Medisch Centrum Groningen
- Medical Research Council (MC_PC_12009)
- Topics
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
- Keywords
- asthma, goblet cell hyperplasia, tissue-resident memory T cells, Th2 cells, type 2 cytokines, cell-cell interactions, CD4+ T cells, upper and lower airways, lung parenchyma, mucosal immunity, lung homeostasis
- MeSH terms
- Adult, Aged, Asthma, Cell Communication, Epithelial Cells, Female, Humans, Lung, Male, Metaplasia, Middle Aged, CD4-Positive T-Lymphocytes, Th2 Cells, Goblet Cells, Genome-Wide Association Study, Transcriptome
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