Does the human placenta express the canonical cell entry mediators for SARS-CoV-2?

  1. Roger Pique-Regi  Is a corresponding author
  2. Roberto Romero  Is a corresponding author
  3. Adi L Tarca
  4. Francesca Luca
  5. Yi Xu
  6. Adnan Alazizi
  7. Yaozhu Leng
  8. Chaur-Dong Hsu
  9. Nardhy Gomez-Lopez  Is a corresponding author
  1. Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services, United States
  2. Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, United States
  3. Department of Obstetrics and Gynecology, Wayne State University School of Medicine, United States
  4. Department of Obstetrics and Gynecology, University of Michigan, United States
  5. Department of Epidemiology and Biostatistics, Michigan State University, United States
  6. Detroit Medical Center, United States
  7. Department of Obstetrics and Gynecology, Florida International University, United States
  8. Department of Computer Science, Wayne State University College of Engineering, United States
  9. Department of Physiology, Wayne State University School of Medicine, United States
  10. Department of Biochemistry, Microbiology and Immunology, Wayne State University School of Medicine, United States

Peer review process

This article was accepted for publication as part of eLife's original publishing model.

History

  1. Version of Record updated
  2. Version of Record published
  3. Accepted Manuscript published
  4. Accepted
  5. Received

Decision letter

  1. Stephen CJ Parker
    Reviewing Editor; University of Michigan, United States
  2. Marianne E Bronner
    Senior Editor; California Institute of Technology, United States

In the interests of transparency, eLife publishes the most substantive revision requests and the accompanying author responses.

Acceptance summary:

We believe this timely manuscript fills a critical gap in understanding vertical transmission biology of SARS-CoV-2 and other viruses. These results will help form the foundation for a broad network of single cell/nucleus profiles that can collectively help to dissect mechanisms relevant to the current pandemic. Thank you for the quick scientific progress from your team.

Decision letter after peer review:

Thank you for submitting your article "Does the human placenta express the canonical cell entry mediators for SARS-CoV-2?" for consideration by eLife. Your article has been reviewed by two peer reviewers, one of whom is a member of our Board of Reviewing Editors, and the evaluation has been overseen by Marianne Bronner as the Senior Editor. The reviewers have opted to remain anonymous.

The reviewers have discussed the reviews with one another and the Reviewing Editor has drafted this decision to help you prepare a revised submission.

We would like to draw your attention to changes in our revision policy that we have made in response to COVID-19 (https://elifesciences.org/articles/57162). Specifically, we are asking editors to accept without delay manuscripts, like yours, that they judge can stand as eLife papers without additional data, even if they feel that they would make the manuscript stronger. Thus the revisions requested below only address clarity and presentation.

Summary:

The paper by Pique-Regi and collaborators is of high interest in the current SARS-CoV-2 pandemics, trying to dissect molecular mechanisms behind the apparent lack of placental viral transfer to the fetus. In contrast to ZIka and cytomegalovirus infections in pregnancy, this new coronavirus does not seem to infect pregnant women more than others, nor do they get sicker if infected. Also, a vertical transmission to the fetus seems unlikely, but the molecular mechanisms for this fetal protection are unknown. Therefore, this paper fills an important knowledge gap by its findings of a lacking co-expression of two canonical receptor pathways for SARS-CoV-2 cellular infection (ACE2 and TMPRSS2). Overall, this is a timely and well-written manuscript that fills an important niche in the scientific literature. This is a strong work that only need a few revisions to increase clarity.

Essential revisions:

1) The authors claim that the new snRNA-seq data should help to identify multi-nucleated cells, like STB cells, which they do find in only (or predominantly) in the snRNA-seq data. However, in the UMAP plot in Figure 1A, these cells appear to be in two different clusters that mostly overlap what looks like fibroblasts (in purple) or immune cells (blue, light blue). Some explanation as to why the STB cells appear across these two otherwise distinct clusters would be helpful.

https://doi.org/10.7554/eLife.58716.sa1

Author response

Essential revisions:

1) The authors claim that the new snRNA-seq data should help to identify multi-nucleated cells, like STB cells, which they do find in only (or predominantly) in the snRNA-seq data. However, in the UMAP plot in Figure 1A, these cells appear to be in two different clusters that mostly overlap what looks like fibroblasts (in purple) or immune cells (blue, light blue). Some explanation as to why the STB cells appear across these two otherwise distinct clusters would be helpful.

We thank the reviewers for this comment. The snRNA-seq-derived STB clusters shown in Figure 1A (lime green) appear to be close yet do not completely overlap with the scRNA-seq-derived CTB (dark purple) and npi CTB (green). There is also some but incomplete overlap with NK-cell (dark blue) and T-cell-activated (forest green) clusters, among others, probably as a result of the higher background/soup RNA coming from these cell types. We have added a supplementary figure (Figure 1—figure supplement 1) that displays the high expression of STB specific genes (GH2, CSH1, and CGA) in the STB cluster. We respectfully believe that further investigation into the nature of these two separate clusters is beyond the scope of this article, as there is no co-expression of ACE2 and TMPRSS2 in either of them.

https://doi.org/10.7554/eLife.58716.sa2

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  1. Roger Pique-Regi
  2. Roberto Romero
  3. Adi L Tarca
  4. Francesca Luca
  5. Yi Xu
  6. Adnan Alazizi
  7. Yaozhu Leng
  8. Chaur-Dong Hsu
  9. Nardhy Gomez-Lopez
(2020)
Does the human placenta express the canonical cell entry mediators for SARS-CoV-2?
eLife 9:e58716.
https://doi.org/10.7554/eLife.58716

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https://doi.org/10.7554/eLife.58716