The Spatial and Cell-Type Distribution of SARS-CoV-2 Receptor ACE2 in the Human and Mouse Brains

  1. Rongrong Chen
  2. Keer Wang
  3. Jie Yu
  4. Derek Howard
  5. Leon French
  6. Zhong Chen
  7. Chengping Wen
  8. Zhenghao Xu

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Abstract

By engaging angiotensin-converting enzyme 2 (ACE2 or Ace2), the novel pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) invades host cells and affects many organs, including the brain. However, the distribution of ACE2 in the brain is still obscure. Here, we investigated the ACE2 expression in the brain by analyzing data from publicly available brain transcriptome databases. According to our spatial distribution analysis, ACE2 was relatively highly expressed in some brain locations, such as the choroid plexus and paraventricular nuclei of the thalamus. According to cell-type distribution analysis, nuclear expression of ACE2 was found in many neurons (both excitatory and inhibitory neurons) and some non-neuron cells (mainly astrocytes, oligodendrocytes, and endothelial cells) in the human middle temporal gyrus and posterior cingulate cortex. A few ACE2-expressing nuclei were found in a hippocampal dataset, and none were detected in the prefrontal cortex. Except for the additional high expression of Ace2 in the olfactory bulb areas for spatial distribution as well as in the pericytes and endothelial cells for cell-type distribution, the distribution of Ace2 in the mouse brain was similar to that in the human brain. Thus, our results reveal an outline of ACE2/Ace2 distribution in the human and mouse brains, which indicates that the brain infection of SARS-CoV-2 may be capable of inducing central nervous system symptoms in coronavirus disease 2019 (COVID-19) patients. Potential species differences should be considered when using mouse models to study the neurological effects of SARS-CoV-2 infection.

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  1. Version published to 10.3389/fneur.2020.573095
  2. Version published to 10.1101/2020.04.07.030650v3 on bioRxiv
  3. ScreenIT

    SciScore for 10.1101/2020.04.07.030650: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementCompliance with ethical standards Ethics approval Not Applicable.Randomizationnot detected.Blindingnot detected.Power Analysisnot detected.Sex as a biological variableMouse 2 female , 4 https://singlecell.broadinstitute. male , ( 60 org/single_cell/study/SCP795 days ) Prefrontal cortex Habib et al. , and 2017 [ 20 ] DroNc-Seq

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Species n ( age ) Source Human https://celltypes.brain-map.org/r n=8 ( 24–66 ) naseq/human/mtg Human n=20 https://singlecell.broadinstitute. ( >65 ) org/single_cell/study/SCP371 Human https://singlecell.broadinstitute. n=5 ( 40–65 ) org/single_cell/study/SCP90/ Hippocampus Whole cortex Ding et al. , 10x Chromium , 2019 [ 21 ] SMART-seq2 , DroNc-seq and Mouse 13783 ( one month old ) sci-RNA-seq https://singlecell.broadinstitute. org/single_cell/study/SCP425/ U19 - Huang SNr , SNc , VTA BICCN data ( 1U19MH11482
    Human
    suggested: None
    substantia nigra pars reticulate; SNc: substantia nigra pars compacta; VTA: ventral tegmental area; Spatial and cell-type distribution of Ace2 in mouse brain Allen mouse brain atlas database ( http://mouse.brain-map.org ) was used to analyze the general spatial distribution of Ace2 in the mouse brain .
    http://mouse.brain-map.org
    suggested: (ABA Mouse Brain: Atlas, SCR_017479)
    The data from the Allen human brain atlas database and Allen Cell Types Database was exported to Microsoft Excel 2017 and GraphPad Prism 6.0 for further analysis .
    Microsoft Excel
    suggested: (Microsoft Excel, SCR_016137)
          <div style="margin-bottom:8px">
        <div><b>GraphPad</b></div>
        <div>suggested: (GraphPad Prism, <a href="https://scicrunch.org/resources/Any/search?q=SCR_002798">SCR_002798</a>)</div>
      </div>
    </td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">Acknowledgments We would like to thank the Allen Institute for Brain Science ( https://alleninstitute.org/)</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>https://alleninstitute.org/</b></div>
        <div>suggested: (Allen Institute, <a href="https://scicrunch.org/resources/Any/search?q=SCR_005435">SCR_005435</a>)</div>
      </div>
    </td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">, BRAIN Initiative Cell Census Network ( BICCN , https://biccn.org/) , GTExportal database ( https://www.gtexportal.org) , Human Brain Transcriptome database ( https://hbatlas.org) , and Single Cell Portal database (</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>BICCN</b></div>
        <div>suggested: (BICCN, <a href="https://scicrunch.org/resources/Any/search?q=SCR_015820">SCR_015820</a>)</div>
      </div>
    
      <div style="margin-bottom:8px">
        <div><b>https://biccn.org/</b></div>
        <div>suggested: (BRAIN Cell Data Center, <a href="https://scicrunch.org/resources/Any/search?q=SCR_017266">SCR_017266</a>)</div>
      </div>
    </td></tr></table>

    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).

    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 is not a substitute for expert review. SciScore checks for the presence and correctness of RRIDs (research resource identifiers) in the manuscript, and detects sentences that appear to be missing RRIDs. SciScore also checks to make sure that rigor criteria are addressed by authors. It does this by detecting sentences that discuss criteria such as blinding or power analysis. SciScore does not guarantee that the rigor criteria that it detects are appropriate for the particular study. Instead it assists authors, editors, and reviewers by drawing attention to sections of the manuscript that contain or should contain various rigor criteria and key resources. For details on the results shown here, including references cited, please follow this link.

  4. Version published to 10.1101/2020.04.07.030650v2 on bioRxiv
  5. Version published to 10.1101/2020.04.07.030650v1 on bioRxiv