Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses

  1. Furong Qi
  2. Shen Qian
  3. Shuye Zhang
  4. Zheng Zhang

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Abstract

The new coronavirus (2019-nCoV) outbreak from December 2019 in Wuhan, Hubei, China, has been declared a global public health emergency. Angiotensin I converting enzyme 2 (ACE2), is the host receptor by 2019-nCov to infect human cells. Although ACE2 is reported to be expressed in lung, liver, stomach, ileum, kidney and colon, its expressing levels are rather low, especially in the lung. 2019-nCoV may use co-receptors/auxiliary proteins as ACE2 partner to facilitate the virus entry. To identify the potential candidates, we explored the single cell gene expression atlas including 119 cell types of 13 human tissues and analyzed the single cell co-expression spectrum of 51 reported RNA virus receptors and 400 other membrane proteins. Consistent with other recent reports, we confirmed that ACE2 was mainly expressed in lung AT2, liver cholangiocyte, colon colonocytes, esophagus keratinocytes, ileum ECs, rectum ECs, stomach epithelial cells, and kidney proximal tubules. Intriguingly, we found that the candidate co-receptors, manifesting the most similar expression patterns with ACE2 across 13 human tissues, are all peptidases, including ANPEP, DPP4 and ENPEP. Among them, ANPEP and DPP4 are the known receptors for human CoVs, suggesting ENPEP as another potential receptor for human CoVs. We also conducted “CellPhoneDB” analysis to understand the cell crosstalk between CoV-targets and their surrounding cells across different tissues. We found that macrophages frequently communicate with the CoVs targets through chemokine and phagocytosis signaling, highlighting the importance of tissue macrophages in immune defense and immune pathogenesis.

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    SciScore for 10.1101/2020.02.16.951913: (What is this?)

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

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Data collection: The gene raw counts or normalized gene expression matrix for each single cell were downloaded from GEO (https://www.ncbi.nlm.nih.gov/geo/) or Human Cell Atlas (https://www.humancellatlas.org) database (Table S1).
    https://www.ncbi.nlm.nih.gov/geo/
    suggested: (Gene Expression Omnibus (GEO, RRID:SCR_005012)
    https://www.humancellatlas.org
    suggested: (Human Cell Atlas, RRID:SCR_016530)
    It was implemented by ‘‘FindVariableGenes’’ function in the Seurat package.
    Seurat
    suggested: (SEURAT, RRID:SCR_007322)
    Cell-cell interaction analysis: We conducted cell-cell interaction analysis utilizing cellphonedb function curated by CellPhoneDB database[24].
    CellPhoneDB
    suggested: (CellPhoneDB, RRID:SCR_017054)

    Results from OddPub: Thank you for sharing your data.

    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

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  2. Version published to 10.1101/2020.02.16.951913 on bioRxiv