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SARS-CoV-2 receptor ACE2 and TMPRSS2 are predominantly expressed in a transient secretory cell type in subsegmental bronchial branches

View ORCID ProfileSoeren Lukassen, Robert Lorenz Chua, Timo Trefzer, Nicolas C. Kahn, Marc A. Schneider, Thomas Muley, Hauke Winter, Michael Meister, Carmen Veith, Agnes W. Boots, Bianca P. Hennig, Michael Kreuter, Christian Conrad, Roland Eils
doi: https://doi.org/10.1101/2020.03.13.991455
Soeren Lukassen
1Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany
2Berlin Institute of Health (BIH), Center for Digital Health, Anna-Louisa-Karsch-Strasse 2, 10178 Berlin, Germany
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  • ORCID record for Soeren Lukassen
Robert Lorenz Chua
1Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany
2Berlin Institute of Health (BIH), Center for Digital Health, Anna-Louisa-Karsch-Strasse 2, 10178 Berlin, Germany
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Timo Trefzer
1Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany
2Berlin Institute of Health (BIH), Center for Digital Health, Anna-Louisa-Karsch-Strasse 2, 10178 Berlin, Germany
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Nicolas C. Kahn
3Thoraxklinik, Heidelberg University Hospital, Department of Pneumology and Critical Care Medicine, Roentgenstrasse 1, 69126 Heidelberg, Germany
4Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research (DZL), Im Neuenheimer Feld 156, 69120 Heidelberg, Germany
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Marc A. Schneider
4Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research (DZL), Im Neuenheimer Feld 156, 69120 Heidelberg, Germany
5Thoraxklinik, Heidelberg University Hospital, Translational Research Unit, Roentgenstrasse 1, 69126 Heidelberg, Germany
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Thomas Muley
4Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research (DZL), Im Neuenheimer Feld 156, 69120 Heidelberg, Germany
5Thoraxklinik, Heidelberg University Hospital, Translational Research Unit, Roentgenstrasse 1, 69126 Heidelberg, Germany
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Hauke Winter
4Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research (DZL), Im Neuenheimer Feld 156, 69120 Heidelberg, Germany
6Thoraxklinik, Heidelberg University Hospital, Department of Thoracic Surgery, Roentgenstrasse 1, 69126 Heidelberg, Germany
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Michael Meister
4Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research (DZL), Im Neuenheimer Feld 156, 69120 Heidelberg, Germany
5Thoraxklinik, Heidelberg University Hospital, Translational Research Unit, Roentgenstrasse 1, 69126 Heidelberg, Germany
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Carmen Veith
7Division of Redox Regulation, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
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Agnes W. Boots
8Department of Pharmacology and Toxicology, NUTRIM School of Nutrition, Translational Research and Metabolism. Faculty of Health, Medicine and Life Sciences, Maastricht University, Universiteitssingel 50, Maastricht, the Netherlands
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Bianca P. Hennig
1Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany
2Berlin Institute of Health (BIH), Center for Digital Health, Anna-Louisa-Karsch-Strasse 2, 10178 Berlin, Germany
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Michael Kreuter
3Thoraxklinik, Heidelberg University Hospital, Department of Pneumology and Critical Care Medicine, Roentgenstrasse 1, 69126 Heidelberg, Germany
4Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research (DZL), Im Neuenheimer Feld 156, 69120 Heidelberg, Germany
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  • For correspondence: roland.eils@bihealth.de christian.conrad@bihealth.de kreuter@uni-heidelberg.de
Christian Conrad
1Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany
2Berlin Institute of Health (BIH), Center for Digital Health, Anna-Louisa-Karsch-Strasse 2, 10178 Berlin, Germany
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  • For correspondence: roland.eils@bihealth.de christian.conrad@bihealth.de kreuter@uni-heidelberg.de
Roland Eils
1Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany
2Berlin Institute of Health (BIH), Center for Digital Health, Anna-Louisa-Karsch-Strasse 2, 10178 Berlin, Germany
9Health Data Science Unit, Heidelberg University Hospital and BioQuant, Im Neuenheimer Feld 267, 69120 Heidelberg, Germany
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  • For correspondence: roland.eils@bihealth.de christian.conrad@bihealth.de kreuter@uni-heidelberg.de
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SUMMARY

The SARS-CoV-2 pandemic affecting the human respiratory system severely challenges public health and urgently demands for increasing our understanding of COVID-19 pathogenesis, especially host factors facilitating virus infection and replication. SARS-CoV-2 was reported to enter cells via binding to ACE2, followed by its priming by TMPRSS2. Here, we investigate ACE2 and TMPRSS2 expression levels and their distribution across cell types in lung tissue (twelve donors, 39,778 cells) and in cells derived from subsegmental bronchial branches (four donors, 17,521 cells) by single nuclei and single cell RNA sequencing, respectively. While TMPRSS2 is expressed in both tissues, in the subsegmental bronchial branches ACE2 is predominantly expressed in a transient secretory cell type. Interestingly, these transiently differentiating cells show an enrichment for pathways related to RHO GTPase function and viral processes suggesting increased vulnerability for SARS-CoV-2 infection. Our data provide a rich resource for future investigations of COVID-19 infection and pathogenesis.

Footnotes

  • Corrected labels in supplementary figures; updated acknowledgments section.

  • https://doi.org/10.6084/m9.figshare.11981034.v1

  • https://data.mendeley.com/datasets/7r2cwbw44m/1

Copyright 
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 4.0 International license.
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Posted March 30, 2020.
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SARS-CoV-2 receptor ACE2 and TMPRSS2 are predominantly expressed in a transient secretory cell type in subsegmental bronchial branches
Soeren Lukassen, Robert Lorenz Chua, Timo Trefzer, Nicolas C. Kahn, Marc A. Schneider, Thomas Muley, Hauke Winter, Michael Meister, Carmen Veith, Agnes W. Boots, Bianca P. Hennig, Michael Kreuter, Christian Conrad, Roland Eils
bioRxiv 2020.03.13.991455; doi: https://doi.org/10.1101/2020.03.13.991455
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SARS-CoV-2 receptor ACE2 and TMPRSS2 are predominantly expressed in a transient secretory cell type in subsegmental bronchial branches
Soeren Lukassen, Robert Lorenz Chua, Timo Trefzer, Nicolas C. Kahn, Marc A. Schneider, Thomas Muley, Hauke Winter, Michael Meister, Carmen Veith, Agnes W. Boots, Bianca P. Hennig, Michael Kreuter, Christian Conrad, Roland Eils
bioRxiv 2020.03.13.991455; doi: https://doi.org/10.1101/2020.03.13.991455

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