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Single-cell analysis of human lung epithelia reveals concomitant expression of the SARS-CoV-2 receptor ACE2 with multiple virus receptors and scavengers in alveolar type II cells
Guangchun Han; Ansam Sinjab; Warapen Treekitkarnmongkol; Patrick Brennan; Kieko Hara; Kyle Chang; Elena Bogatenkova; Beatriz Sanchez-Espiridion; Carmen Behrens; Boning Gao; Luc Girard; Jianjun Zhang; Boris Sepesi; Tina Cascone; Lauren Byers; Don L. Gibbons; Jichao Chen; Seyed Javad Moghaddam; Edwin J. Ostrin; Junya Fujimoto; Jerry Shay; John V. Heymach; John D. Minna; Steven Dubinett; Paul A. Scheet; Ignacio I. Wistuba; Edward Hill; Shannon Telesco; Christopher Stevenson; Avrum E. Spira; Linghua Wang; Humam Kadara.
Affiliation
  • Guangchun Han; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
  • Ansam Sinjab; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
  • Warapen Treekitkarnmongkol; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
  • Patrick Brennan; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
  • Kieko Hara; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
  • Kyle Chang; Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
  • Elena Bogatenkova; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
  • Beatriz Sanchez-Espiridion; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
  • Carmen Behrens; Department of Thoracic, Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
  • Boning Gao; Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern, Dallas, TX, USA
  • Luc Girard; Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern, Dallas, TX, USA
  • Jianjun Zhang; Department of Thoracic, Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
  • Boris Sepesi; Department of Cardiovascular and Thoracic Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
  • Tina Cascone; Department of Thoracic, Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
  • Lauren Byers; Department of Thoracic, Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
  • Don L. Gibbons; Department of Thoracic, Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
  • Jichao Chen; Department of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
  • Seyed Javad Moghaddam; Department of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
  • Edwin J. Ostrin; Department of General Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
  • Junya Fujimoto; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
  • Jerry Shay; Department of Cell Biology, University of Texas Southwestern, Dallas, TX, USA
  • John V. Heymach; Department of Thoracic, Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
  • John D. Minna; Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern, Dallas, TX, USA
  • Steven Dubinett; Department of Medicine, The University of California Los Angeles, Los Angeles, CA, USA
  • Paul A. Scheet; Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
  • Ignacio I. Wistuba; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
  • Edward Hill; Lung Cancer Initiative at Johnson and Johnson, Lansdale, PA, USA
  • Shannon Telesco; Lung Cancer Initiative at Johnson and Johnson, Lansdale, PA, USA
  • Christopher Stevenson; Lung Cancer Initiative at Johnson and Johnson, Lansdale, PA, USA
  • Avrum E. Spira; Lung Cancer Initiative at Johnson and Johnson, Lansdale, PA, USA and Section of Computational Biomedicine, Boston University, Boston, MA, USA
  • Linghua Wang; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
  • Humam Kadara; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
Preprint in English | bioRxiv | ID: ppbiorxiv-045617
ABSTRACT
The novel coronavirus SARS-CoV-2 was identified as the causative agent of the ongoing pandemic COVID 19. COVID-19-associated deaths are mainly attributed to severe pneumonia and respiratory failure. Recent work demonstrated that SARS-CoV-2 binds to angiotensin converting enzyme 2 (ACE2) in the lung. To better understand ACE2 abundance and expression patterns in the lung we interrogated our in-house single-cell RNA-sequencing dataset containing 70,085 EPCAM+ lung epithelial cells from paired normal and lung adenocarcinoma tissues. Transcriptomic analysis revealed a diverse repertoire of airway lineages that included alveolar type I and II, bronchioalveolar, club/secretory, quiescent and proliferating basal, ciliated and malignant cells as well as rare populations such as ionocytes. While the fraction of lung epithelial cells expressing ACE2 was low (1.7% overall), alveolar type II (AT2, 2.2% ACE2+) cells exhibited highest levels of ACE2 expression among all cell subsets. Further analysis of the AT2 compartment (n = 27,235 cells) revealed a number of genes co-expressed with ACE2 that are important for lung pathobiology including those associated with chronic obstructive pulmonary disease (COPD; HHIP), pneumonia and infection (FGG and C4BPA) as well as malarial/bacterial (CD36) and viral (DMBT1) scavenging which, for the most part, were increased in smoker versus light or non-smoker cells. Notably, DMBT1 was highly expressed in AT2 cells relative to other lung epithelial subsets and its expression positively correlated with ACE2. We describe a population of ACE2-positive AT2 cells that co-express pathogen (including viral) receptors (e.g. DMBT1) with crucial roles in host defense thus comprising plausible phenotypic targets for treatment of COVID-19.
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Full text: Available Collection: Preprints Database: bioRxiv Language: English Year: 2020 Document type: Preprint
Fulltext
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Full text: Available Collection: Preprints Database: bioRxiv Language: English Year: 2020 Document type: Preprint