The SARS-CoV-2 receptor ACE2 expression of maternal-fetal interface and fetal organs by single-cell transcriptome study

Original Article: Li M, Chen L, Zhang J, Xiong C, Li X. The SARS-CoV-2 receptor ACE2 expression of maternal-fetal interface and fetal organs by single-cell transcriptome study. PLoS One. 2020;15(4):e0230295. Published 2020 Apr 16.

Author of summary: Federica Fontanella; Reviewer: Dimitrios Spiliotopoulos

Original Article Published on April 16th, 2020

In this study, cell-specific expression of ACE2 in maternal-fetal interface and in multiple fetal organs has been assessed. Single-cell RNA sequencing data indicate that ACE2 is highly expressed in maternal-fetal interface cells such as stromal, perivascular cells of decidua, cytotrophoblast and syncytiotrophoblast. Concerning fetal organs, ACE2 was expressed in human fetal heart, liver and lung, but not in kidney. Overall, the SARS-CoV-2 receptor is widely expressed in specific cell types of maternal-fetal interface and fetal organs. Therefore, both the vertical transmission and the placenta dysfunction/abortion caused by SARS-CoV-2 need to be further carefully investigated in clinical practice.

Introduction:

Potential vertical transmission of SARS-CoV-2 remains controversial. Considering that:

  • members of the coronavirus family (MERS-CoV, SARS-CoV) may constitute a risk during pregnancy
  • SARS-CoV-2 shares the same host receptor as SARS-CoV (79% sequence identity between the viruses), the Angiotensin-converting enzyme 2 (ACE2)
  • the serine protease for virus Spike protein priming, TMPRSS2 is indispensable for cell entry of SARS-CoV-2.

may SARS-CoV-2 potentially transmit vertically to the fetus in pregnant women?

Aim & Methods:

Expression of ACE2 and TMPRSS2 in maternal-fetal interface and different fetal organs has been evaluated by using scRNA-seq data.

Results:

  • Expression of ACE2/TMPRSS2 in maternal fetal interface:
    • ACE2 was expressed in 4 cell types out of the 32 considered: stromal cells, perivascular cells in decidua, villous cytotrophoblast and syncytiotrophoblast in placenta.
    • TMPRSS2 was expressed in villous cytotrophoblast and epithelial glandular cells, and presented low expression in syncytiotrophoblast.
    • Expression of ACE2 in extravillous trophoblast was extremely low level in early placentas (8 weeks) and higher at later stage in pregnancy (24 weeks). A similar dynamic was also found for TMPRSS2 expression
    • Overall, maternal-fetal interface data seem to show that ACE2 and TMPRSS2 are co-expressed in villous cytotrophoblast, syncytiotrophoblast and extravillous trophoblast cells, and their expression level may increase
  • Expression of ACE2/TMPRSS2 inhuman fetal organs (heart, lungs, liver, and kidneys):
    • Expression of ACE2 was abundant, while expression of TMPRSS2 was moderate.
    • ACE2 was expressed in fetal heart in cardiomyocytes (which also express TMPRSS2), macrophages, smooth muscle cells and pericytes; and in erythroid cells, fibroblasts and hepatocytes in fetal liver. ACE2 expression was not observed in fetal kidneys.  
    • ACE2 and TMPRSS2 were highly expressed in airway epithelial cell and arterial endothelial cells at post-natal day 1, suggesting a high risk of airborne infection of newborns.
  • Dynamic expression of ACE2 in fetal and neonatal mouse lung:
    • Consistently with human fetal lung, ACE2 and TMPRSS2 were highly expressed in airway epithelial cells in late pregnancy stage.
    • Expression of ACE2 was higher during the first postnatal days than later in life or during fetal phase. This suggests that new-born might be particularly vulnerable to SARS-CoV2, as in humans.

NB: Mouse lung cell atlas from late pregnancy have been studied as cell atlas of human fetal lung is unavailable

Conclusions:

SARS-CoV-2 receptor is widely expressed in specific cell-types of maternal-fetal interface and fetal organs. Therefore, both vertical transmission and placental dysfunction caused by SARS-CoV-2 need to be further carefully investigated in clinical practice.

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