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

  1. Guangchun Han
  2. Ansam Sinjab
  3. Warapen Treekitkarnmongkol
  4. Patrick Brennan
  5. Kieko Hara
  6. Kyle Chang
  7. Elena Bogatenkova
  8. Beatriz Sanchez-Espiridion
  9. Carmen Behrens
  10. Boning Gao
  11. Luc Girard
  12. Jianjun Zhang
  13. Boris Sepesi
  14. Tina Cascone
  15. Lauren Byers
  16. Don L. Gibbons
  17. Jichao Chen
  18. Seyed Javad Moghaddam
  19. Edwin J. Ostrin
  20. Junya Fujimoto
  21. Jerry Shay
  22. John V. Heymach
  23. John D. Minna
  24. Steven Dubinett
  25. Paul A. Scheet
  26. Ignacio I. Wistuba
  27. Edward Hill
  28. Shannon Telesco
  29. Christopher Stevenson
  30. Avrum E. Spira
  31. Linghua Wang
  32. Humam Kadara

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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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    SciScore for 10.1101/2020.04.16.045617: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementConsent: All patients were evaluated at the University of Texas MD Anderson Cancer Center (MD Anderson) and had provided informed consents under approved institutional review board protocols.
    IRB: All patients were evaluated at the University of Texas MD Anderson Cancer Center (MD Anderson) and had provided informed consents under approved institutional review board protocols.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Differentially expressed genes (DEGs) for each cell cluster were identified using the FindAllMarkers function in Seurat R package.
    Seurat
    suggested: (SEURAT, RRID:SCR_007322)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • No funding statement was detected.
    • No protocol registration statement was detected.

    About SciScore

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  2. Version published to 10.1101/2020.04.16.045617v1 on bioRxiv