ACE2-expressing endothelial cells in aging mouse brain

  1. Su Bin Lim
  2. Valina L. Dawson
  3. Ted M. Dawson
  4. Sung-Ung Kang

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Abstract

Angiotensin-converting enzyme 2 (ACE2) is a key receptor mediating the entry of SARS-CoV-2 into the host cell. Through a systematic analysis of publicly available mouse brain sc/snRNA-seq data, we found that ACE2 is specifically expressed in small sub-populations of endothelial cells and mural cells, namely pericytes and vascular smooth muscle cells. Further, functional changes in viral mRNA transcription and replication, and impaired blood-brain barrier regulation were most prominently implicated in the aged, ACE2-expressing endothelial cells, when compared to the young adult mouse brains. Concordant EC transcriptomic changes were further found in normal aged human brains. Overall, this work reveals an outline of ACE2 distribution in the mouse brain and identify putative brain host cells that may underlie the selective susceptibility of the aging brain to viral infection.

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  1. ScreenIT

    SciScore for 10.1101/2020.07.11.198770: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Genes with |logGER (Gene Expression Ratio)|>0.1 and FDR<0.05 were defined as DEGs, and were analyzed for functional pathway enrichment using GeneAnalyics (https://geneanalytics.genecards.org/).
    GeneAnalyics
    suggested: None
    The R qvalue package [24] from Bioconductor was used to assess the performance of q-value approach.
    Bioconductor
    suggested: (Bioconductor, RRID:SCR_006442)
    The R biomaRt package [25] from Bioconductor was used to convert mouse EC DEGs to human gene symbols (hgnc) using getLDS() function.
    biomaRt
    suggested: (biomaRt, RRID:SCR_019214)
    Gene Set Enrichment Analysis (GSEA v4.0.3; https://www.gsea-msigdb.org/gsea/index.jsp) [26] was used to assess EC DEGs (EC up- and down-regulated genes) in GTEx human brain bulk RNA-seq samples.
    GSEA
    suggested: (SeqGSEA, RRID:SCR_005724)

    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

    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 10.1101/2020.07.11.198770v1 on bioRxiv