Tata, P. R. & Rajagopal, J. Plasticity in the lung: making and breaking cell identity. Development 144, 755–766 (2017).
Macosko, E. Z. et al. Highly parallel genome-wide expression profiling of individual cells using nanoliter droplets. Cell 161, 1202–1214 (2015).
Montoro, D. T. et al. A revised airway epithelial hierarchy includes CFTR-expressing ionocytes. Nature 560, 319–324 (2018).
Plasschaert, L. W. et al. A single-cell atlas of the airway epithelium reveals the CFTR-rich pulmonary ionocyte. Nature 560, 377–381 (2018).
Bisset, L. R. & Schmid-Grendelmeier, P. Chemokines and their receptors in the pathogenesis of allergic asthma: progress and perspective. Curr. Opin. Pulm. Med. 11, 35–42 (2005).
Colvin, R. A. et al. Synaptotagmin-mediated vesicle fusion regulates cell migration. Nat. Immunol. 11, 495–502 (2010).
Urawa, M. et al. Protein S is protective in pulmonary fibrosis. J. Thromb. Haemost. 14, 1588–1599 (2016).
Wujak, A. et al. FXYD1 negatively regulates Na+/K+-ATPase activity in lung alveolar epithelial cells. Respir. Physiol. Neurobiol. 220, 54–61 (2016).
Krotova, K. et al. Alpha-1 antitrypsin-deficient macrophages have increased matriptase-mediated proteolytic activity. Am. J. Respir. Cell Mol. Biol. 57, 238–247 (2017).
Vogl, T. et al. S100A12 is expressed exclusively by granulocytes and acts independently from MRP8 and MRP14. J. Biol. Chem. 274, 25291–25296 (1999).
Mitchell, A. et al. LILRA5 is expressed by synovial tissue macrophages in rheumatoid arthritis, selectively induces pro-inflammatory cytokines and IL-10 and is regulated by TNF-α, IL-10 and IFN-γ. Eur. J. Immunol. 38, 3459–3473 (2008).
Condon, T. V., Sawyer, R. T., Fenton, M. J. & Riches, D. W. H. Lung dendritic cells at the innate-adaptive immune interface. J. Leukoc. Biol. 90, 883–895 (2011).
Baumann, U., Routes, J. M., Soler-Palacín, P. & Jolles, S. The lung in primary immunodeficiencies: new concepts in infection and inflammation. Front. Immunol. 9, 1837 (2018).
Holgate, S. T. et al. Asthma. Nat. Rev. Dis. Primers 1, 15025 (2015).
Lopez-Guisa, J. M. et al. Airway epithelial cells from asthmatic children differentially express proremodeling factors. J. Allergy Clin. Immunol. 129, 990–997.e6 (2012).
Alcala, S. E. et al. Mitotic asynchrony induces transforming growth factor-β1 secretion from airway epithelium. Am. J. Respir. Cell Mol. Biol. 51, 363–369 (2014).
Harkness, L. M., Ashton, A. W. & Burgess, J. K. Asthma is not only an airway disease, but also a vascular disease. Pharmacol. Ther. 148, 17–33 (2015).
Balzar, S. et al. Mast cell phenotype, location, and activation in severe asthma. Data from the Severe Asthma Research Program. Am. J. Respir. Crit. Care Med. 183, 299–309 (2011).
Truyen, E. et al. Evaluation of airway inflammation by quantitative Th1/Th2 cytokine mRNA measurement in sputum of asthma patients. Thorax 61, 202–208 (2006).
Trapnell, C. et al. The dynamics and regulators of cell fate decisions are revealed by pseudotemporal ordering of single cells. Nat. Biotechnol. 32, 381–386 (2014).
Erle, D. J. & Sheppard, D. The cell biology of asthma. J. Cell Biol. 205, 621–631 (2014).
Danahay, H. et al. Notch2 is required for inflammatory cytokine-driven goblet cell metaplasia in the lung. Cell Rep. 10, 239–252 (2015).
Gomi, K., Arbelaez, V., Crystal, R. G. & Walters, M. S. Activation of NOTCH1 or NOTCH3 signaling skews human airway basal cell differentiation toward a secretory pathway. PLoS ONE 10, e0116507 (2015).
Ordovas-Montanes, J. et al. Allergic inflammatory memory in human respiratory epithelial progenitor cells. Nature 560, 649–654 (2018).
Luo, W. et al. Airway epithelial expression quantitative trait loci reveal genes underlying asthma and other airway diseases. Am. J. Respir. Cell Mol. Biol. 54, 177–187 (2016).
Wu, C. A. et al. Bronchial epithelial cells produce IL-5: implications for local immune responses in the airways. Cell. Immunol. 264, 32–41 (2010).
Laitinen, L. A., Laitinen, A. & Haahtela, T. Airway mucosal inflammation even in patients with newly diagnosed asthma. Am. Rev. Respir. Dis. 147, 697–704 (1993).
Arima, M. & Fukuda, T. Prostaglandin D2 and TH2 inflammation in the pathogenesis of bronchial asthma. Korean J. Intern. Med. 26, 8–18 (2011).
Xue, L. et al. Prostaglandin D2 activates group 2 innate lymphoid cells through chemoattractant receptor-homologous molecule expressed on TH2 cells. J. Allergy Clin. Immunol. 133, 1184–1194 (2014).
Dougherty, R. H. et al. Accumulation of intraepithelial mast cells with a unique protease phenotype in TH2-high asthma. J. Allergy Clin. Immunol. 125, 1046–1053.e8 (2010).
Hol, B. E., van de Graaf, E. A., Out, T. A., Hische, E. A. & Jansen, H. M. IgM in the airways of asthma patients. Int. Arch. Allergy Appl. Immunol. 96, 12–18 (1991).
Muehling, L. M., Lawrence, M. G. & Woodfolk, J. A. Pathogenic CD4+ T cells in patients with asthma. J. Allergy Clin. Immunol. 140, 1523–1540 (2017).
Oja, A. E. et al. Trigger-happy resident memory CD4+ T cells inhabit the human lungs. Mucosal Immunol. 11, 654–667 (2018).
Mitson-Salazar, A. et al. Hematopoietic prostaglandin D synthase defines a proeosinophilic pathogenic effector human TH2 cell subpopulation with enhanced function. J. Allergy Clin. Immunol. 137, 907–918.e9 (2016).
Wambre, E. et al. A phenotypically and functionally distinct human T H2 cell subpopulation is associated with allergic disorders. Sci. Transl. Med. 9, eaam9171 (2017).
Lam, E. P. S. et al. IL-25/IL-33-responsive TH2 cells characterize nasal polyps with a default TH17 signature in nasal mucosa. J. Allergy Clin. Immunol. 137, 1514–1524 (2016).
Vento-Tormo, R. et al. Single-cell reconstruction of the early maternal–fetal interface in humans. Nature 563, 347–353 (2018).
Weckmann, M., Kopp, M. V., Heinzmann, A. & Mattes, J. Haplotypes covering the TNFSF10 gene are associated with bronchial asthma. Pediatr. Allergy Immunol. 22, 25–30 (2011).
Harada, M. et al. Thymic stromal lymphopoietin gene promoter polymorphisms are associated with susceptibility to bronchial asthma. Am. J. Respir. Cell Mol. Biol. 44, 787–793 (2011).
Grotenboer, N. S., Ketelaar, M. E., Koppelman, G. H. & Nawijn, M. C. Decoding asthma: translating genetic variation in IL33 and IL1RL1 into disease pathophysiology. J. Allergy Clin. Immunol. 131, 856–865 (2013).
Holgate, S. T. et al. Epithelial-mesenchymal communication in the pathogenesis of chronic asthma. Proc. Am. Thorac. Soc. 1, 93–98 (2004).
Heijink, I. H. et al. Down-regulation of E-cadherin in human bronchial epithelial cells leads to epidermal growth factor receptor-dependent Th2 cell-promoting activity. J. Immunol. 178, 7678–7685 (2007).
Song, J. et al. Aberrant DNA methylation and expression of SPDEF and FOXA2 in airway epithelium of patients with COPD. Clin. Epigenetics 9, 42 (2017).
Picelli, S. et al. Full-length RNA-seq from single cells using Smart-seq2. Nat. Protoc. 9, 171–181 (2014).
Wu, T. D. & Nacu, S. Fast and SNP-tolerant detection of complex variants and splicing in short reads. Bioinformatics 26, 873–881 (2010).
Dobin, A. et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29, 15–21 (2013).
van den Brink, S. C. et al. Single-cell sequencing reveals dissociation-induced gene expression in tissue subpopulations. Nat. Methods 14, 935–936 (2017).
Young, M. D. & Behjati, S. SoupX removes ambient RNA contamination from droplet based single cell RNA sequencing data. Preprint at https://doi.org/10.1101/303727 (2018).
Wolock, S. L., Lopez, R. & Klein, A. M. Scrublet: computational identification of cell doublets in single-cell transcriptomic data. Cell Syst. 8, P281–291.E9 (2019).
Butler, A., Hoffman, P., Smibert, P., Papalexi, E. & Satija, R. Integrating single-cell transcriptomic data across different conditions, technologies, and species. Nat. Biotechnol. 36, 411–420 (2018).
Mereu, E. et al. matchSCore: matching single-cell phenotypes across tools and experiments. Preprint at https://doi.org/10.1101/314831 (2018).