SARS‐CoV‐2 receptor ACE2 and TMPRSS2 are primarily expressed in bronchial transient secretory cells

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 strongly 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.

Type: Other
Archiver: European Genome-Phenome Archive (EGA)

1 Dataset 5 Publications

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID	Description	Technology	Samples
EGAD00001006185	ALI culture bronchial cells and alveolar lung surgical resection scRNA-Seq	Illumina HiSeq 4000	16

Publications	Citations
SARS-CoV-2 receptor ACE2 and TMPRSS2 are primarily expressed in bronchial transient secretory cells. Lukassen S, Chua RL, Trefzer T, Kahn NC, Schneider MA, Muley T, Winter H, Meister M, Veith C, Boots AW, Hennig BP, Kreuter M, Conrad C, Eils R. EMBO J 39: 2020 e105114	664
Determinants of SARS-CoV-2 entry and replication in airway mucosal tissue and susceptibility in smokers. Nakayama T, Lee IT, Jiang S, Matter MS, Yan CH, Overdevest JB, Wu CT, Goltsev Y, Shih LC, Liao CK, Zhu B, Bai Y, Lidsky P, Xiao Y, Zarabanda D, Yang A, Easwaran M, Schürch CM, Chu P, Chen H, Stalder AK, McIlwain DR, Borchard NA, Gall PA, Dholakia SS, Le W, Xu L, Tai CJ, Yeh TH, Erickson-Direnzo E, Duran JM, Mertz KD, Hwang PH, Haslbauer JD, Jackson PK, Menter T, Andino R, Canoll PD, DeConde AS, Patel ZM, Tzankov A, Nolan GP, Nayak JV. Cell Rep Med 2: 2021 100421	12
SARS-CoV-2 infection triggers profibrotic macrophage responses and lung fibrosis. Wendisch D, Dietrich O, Mari T, von Stillfried S, Ibarra IL, Mittermaier M, Mache C, Chua RL, Knoll R, Timm S, Brumhard S, Krammer T, Zauber H, Hiller AL, Pascual-Reguant A, Mothes R, Bülow RD, Schulze J, Leipold AM, Djudjaj S, Erhard F, Geffers R, Pott F, Kazmierski J, Radke J, Pergantis P, Baßler K, Conrad C, Aschenbrenner AC, Sawitzki B, Landthaler M, Wyler E, Horst D, Deutsche COVID-19 OMICS Initiative (DeCOI), Hippenstiel S, Hocke A, Heppner FL, Uhrig A, Garcia C, Machleidt F, Herold S, Elezkurtaj S, Thibeault C, Witzenrath M, Cochain C, Suttorp N, Drosten C, Goffinet C, Kurth F, Schultze JL, Radbruch H, Ochs M, Eils R, Müller-Redetzky H, Hauser AE, Luecken MD, Theis FJ, Conrad C, Wolff T, Boor P, Selbach M, Saliba AE, Sander LE. Cell 184: 2021 6243-6261.e27	178
Identification of Transcription Factors Regulating SARS-CoV-2 Tropism Factor Expression by Inferring Cell-Type-Specific Transcriptional Regulatory Networks in Human Lungs. Tong H, Chen H, Williams CM. Viruses 14: 2022 837	1
ELF5 is a potential respiratory epithelial cell-specific risk gene for severe COVID-19. Pietzner M, Chua RL, Wheeler E, Jechow K, Willett JDS, Radbruch H, Trump S, Heidecker B, Zeberg H, Heppner FL, Eils R, Mall MA, Richards JB, Sander LE, Lehmann I, Lukassen S, Wareham NJ, Conrad C, Langenberg C. Nat Commun 13: 2022 4484	8