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A cellular census of healthy lung and asthmatic airway wall identifies novel cell states in health and disease

F.A. Vieira Braga, G. Kar, M. Berg, O.A. Carpaij, K. Polanski, L.M. Simon, S. Brouwer, T. Gomes, L. Hesse, J. Jiang, E.S. Fasouli, M. Efremova, R. Vento-Tormo, K. Affleck, S. Palit, P. Strzelecka, H.V. Firth, K.T.A. Mahbubani, A. Cvejic, K.B. Meyer, K. Saeb-Parsy, M. Luinge, C.-A. Brandsma, W. Timens, I. Angelidis, M. Strunz, G.H. Koppelman, A.J. van Oosterhout, H.B. Schiller, F.J. Theis, M. van den Berge, M.C. Nawijn, S.A. Teichmann
doi: https://doi.org/10.1101/527408
F.A. Vieira Braga
1Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SA, United Kingdom.
11Open Targets, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom.
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G. Kar
1Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SA, United Kingdom.
11Open Targets, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom.
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M. Berg
2University of Groningen, University Medical Center Groningen, Department of Pathology & Medical Biology, Groningen, The Netherlands. University of Groningen,
3Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, Groningen, The Netherlands.
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O.A. Carpaij
3Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, Groningen, The Netherlands.
4University Medical Center Groningen, Department of Pulmonology, Groningen, The Netherlands
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K. Polanski
1Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SA, United Kingdom.
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L.M. Simon
5Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Computational Biology, Neuherberg, Germany.
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S. Brouwer
2University of Groningen, University Medical Center Groningen, Department of Pathology & Medical Biology, Groningen, The Netherlands. University of Groningen,
3Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, Groningen, The Netherlands.
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T. Gomes
1Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SA, United Kingdom.
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L. Hesse
2University of Groningen, University Medical Center Groningen, Department of Pathology & Medical Biology, Groningen, The Netherlands. University of Groningen,
3Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, Groningen, The Netherlands.
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J. Jiang
2University of Groningen, University Medical Center Groningen, Department of Pathology & Medical Biology, Groningen, The Netherlands. University of Groningen,
3Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, Groningen, The Netherlands.
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E.S. Fasouli
1Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SA, United Kingdom.
11Open Targets, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom.
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M. Efremova
1Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SA, United Kingdom.
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R. Vento-Tormo
1Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SA, United Kingdom.
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K. Affleck
7Allergic Inflammation Discovery Performance Unit, Respiratory Therapy Area, GlaxoSmithKline, Stevenage, United Kingdom.
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S. Palit
5Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Computational Biology, Neuherberg, Germany.
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P. Strzelecka
1Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SA, United Kingdom.
13Department of Haematology, University of Cambridge, Cambridge, CB2 0XY, UK
14Cambridge Stem Cell Institute, Cambridge CB2 1QR, UK
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H.V. Firth
1Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SA, United Kingdom.
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K.T.A. Mahbubani
6Department of Surgery, University of Cambridge, and NIHR Cambridge Biomedical Research Centre, Cambridge, United Kingdom.
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A. Cvejic
1Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SA, United Kingdom.
13Department of Haematology, University of Cambridge, Cambridge, CB2 0XY, UK
14Cambridge Stem Cell Institute, Cambridge CB2 1QR, UK
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K.B. Meyer
1Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SA, United Kingdom.
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K. Saeb-Parsy
6Department of Surgery, University of Cambridge, and NIHR Cambridge Biomedical Research Centre, Cambridge, United Kingdom.
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M. Luinge
2University of Groningen, University Medical Center Groningen, Department of Pathology & Medical Biology, Groningen, The Netherlands. University of Groningen,
3Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, Groningen, The Netherlands.
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C.-A. Brandsma
2University of Groningen, University Medical Center Groningen, Department of Pathology & Medical Biology, Groningen, The Netherlands. University of Groningen,
3Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, Groningen, The Netherlands.
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W. Timens
2University of Groningen, University Medical Center Groningen, Department of Pathology & Medical Biology, Groningen, The Netherlands. University of Groningen,
3Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, Groningen, The Netherlands.
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I. Angelidis
9Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Lung Biology and Disease, Group Systems Medicine of Chronic Lung Disease, and Translational Lung Research and CPC-M bioArchive, Member of the German Center for Lung Research (DZL), Munich, Germany.
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M. Strunz
9Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Lung Biology and Disease, Group Systems Medicine of Chronic Lung Disease, and Translational Lung Research and CPC-M bioArchive, Member of the German Center for Lung Research (DZL), Munich, Germany.
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G.H. Koppelman
3Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, Groningen, The Netherlands.
10University of Groningen, University Medical Center Groningen, Department of Pediatric Pulmonology and Pediatric Allergology, Beatrix Children’s Hospital, Groningen, The Netherlands.
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A.J. van Oosterhout
7Allergic Inflammation Discovery Performance Unit, Respiratory Therapy Area, GlaxoSmithKline, Stevenage, United Kingdom.
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H.B. Schiller
9Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Lung Biology and Disease, Group Systems Medicine of Chronic Lung Disease, and Translational Lung Research and CPC-M bioArchive, Member of the German Center for Lung Research (DZL), Munich, Germany.
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F.J. Theis
5Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Computational Biology, Neuherberg, Germany.
8Department of Mathematics, Technische Universität München, Munich, Germany.
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M. van den Berge
3Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, Groningen, The Netherlands.
4University Medical Center Groningen, Department of Pulmonology, Groningen, The Netherlands
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M.C. Nawijn
2University of Groningen, University Medical Center Groningen, Department of Pathology & Medical Biology, Groningen, The Netherlands. University of Groningen,
3Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, Groningen, The Netherlands.
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  • For correspondence: m.c.nawijn@umcg.nl st9@sanger.ac.uk
S.A. Teichmann
1Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SA, United Kingdom.
11Open Targets, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom.
12Theory of Condensed Matter Group, Cavendish Laboratory/Dept Physics, University of Cambridge, JJ Thomson Avenue, Cambridge CB3 0EH, UK
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  • For correspondence: m.c.nawijn@umcg.nl st9@sanger.ac.uk
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Summary

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 health. We report location-dependent airway epithelial cell states, and a novel subset of tissue-resident memory T cells. In lower airways of asthma patients, mucous cell hyperplasia is shown to stem from a novel mucous ciliated cell state, as well as goblet cell hyperplasia. We report presence of pathogenic effector Th2 cells in asthma, and find evidence for type-2 cytokines in maintaining the altered epithelial cell states. Unbiased analysis of cell-cell interactions identify a shift from airway structural cell communication in health to a Th2-dominated interactome in asthma.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted January 23, 2019.
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A cellular census of healthy lung and asthmatic airway wall identifies novel cell states in health and disease
F.A. Vieira Braga, G. Kar, M. Berg, O.A. Carpaij, K. Polanski, L.M. Simon, S. Brouwer, T. Gomes, L. Hesse, J. Jiang, E.S. Fasouli, M. Efremova, R. Vento-Tormo, K. Affleck, S. Palit, P. Strzelecka, H.V. Firth, K.T.A. Mahbubani, A. Cvejic, K.B. Meyer, K. Saeb-Parsy, M. Luinge, C.-A. Brandsma, W. Timens, I. Angelidis, M. Strunz, G.H. Koppelman, A.J. van Oosterhout, H.B. Schiller, F.J. Theis, M. van den Berge, M.C. Nawijn, S.A. Teichmann
bioRxiv 527408; doi: https://doi.org/10.1101/527408
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A cellular census of healthy lung and asthmatic airway wall identifies novel cell states in health and disease
F.A. Vieira Braga, G. Kar, M. Berg, O.A. Carpaij, K. Polanski, L.M. Simon, S. Brouwer, T. Gomes, L. Hesse, J. Jiang, E.S. Fasouli, M. Efremova, R. Vento-Tormo, K. Affleck, S. Palit, P. Strzelecka, H.V. Firth, K.T.A. Mahbubani, A. Cvejic, K.B. Meyer, K. Saeb-Parsy, M. Luinge, C.-A. Brandsma, W. Timens, I. Angelidis, M. Strunz, G.H. Koppelman, A.J. van Oosterhout, H.B. Schiller, F.J. Theis, M. van den Berge, M.C. Nawijn, S.A. Teichmann
bioRxiv 527408; doi: https://doi.org/10.1101/527408

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