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. 2020 Apr 16;15(4):e0230295.
doi: 10.1371/journal.pone.0230295. eCollection 2020.

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

Mengmeng Li  1 , Liang Chen  2 , Jingxiao Zhang  3 , Chenglong Xiong  2   4 , Xiangjie Li  3
Affiliations

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

Mengmeng Li et al. PLoS One. .

Abstract

The new type of pneumonia caused by the SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) has been declared as a global public health concern by WHO. As of April 3, 2020, more than 1,000,000 human infections have been diagnosed around the world, which exhibited apparent person-to-person transmission characteristics of this virus. The capacity of vertical transmission in SARS-CoV-2 remains controversial recently. Angiotensin-converting enzyme 2 (ACE2) is now confirmed as the receptor of SARS-CoV-2 and plays essential roles in human infection and transmission. In present study, we collected the online available single-cell RNA sequencing (scRNA-seq) data to evaluate the cell specific expression of ACE2 in maternal-fetal interface as well as in multiple fetal organs. Our results revealed that ACE2 was highly expressed in maternal-fetal interface cells including stromal cells and perivascular cells of decidua, and cytotrophoblast and syncytiotrophoblast in placenta. Meanwhile, ACE2 was also expressed in specific cell types of human fetal heart, liver and lung, but not in kidney. And in a study containing series fetal and post-natal mouse lung, we observed ACE2 was dynamically changed over the time, and ACE2 was extremely high in neonatal mice at post-natal day 1~3. In summary, this study revealed that the SARS-CoV-2 receptor was widely spread in specific cell types of maternal-fetal interface and fetal organs. And thus, both the vertical transmission and the placenta dysfunction/abortion caused by SARS-CoV-2 need to be further carefully investigated in clinical practice.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. The expression level of ACE2 and TMPRSS2 in human placenta.
(A)-(B) are the results from Vento-Tormo, R et al.(2018).[16] (A) The tSNE plots of cell types and ACE2/TMPRSS2 genes. For the right plot, the points colored red are the cells expressed ACE2.(B)The violin plot of ACE2 gene in difference cell types. (C) The expression level of ACE2/TMPRSS2 for the data set from Liu, et al.(2018). DC: dendritic cells; dM: decidual macrophages; dP: decidual perivascular cells; dS: decidual stromal cells; Endo: endothelial cells; Epi: epithelial glandular cells; FB: fibroblasts; HB: Hofbauer cells; PV: perivascular cells; SCT: syncytiotrophoblast; VCT:villous cytotrophoblast; EVT: extravillous trophoblast; CTBs: cytotrophoblast cells; EVTs: extravillous trophoblast cells; STR: villous stromal cells.
Fig 2
Fig 2. The expression level in different organs.
(A) The expression of ACE2/TMPRSS2 in Human fetal Heart. CM-A: Atrial CM cells; CM-V: Ventricle CM cells, EC: Endothelial cdlls; EP: Epithelial cells; SMC: smooth muscle cells; Peri: Pericyte cells; 5W: 5 weeks cells. (B) The expression of ACE2 across different cell types in Human fetal liver. MEMP: mega-karyocyte–erythroid–mast cell progenitor; DC: dendritic cells. NK: Nature killer cells (C) The expression of ACE2/TMPRSS2 across different PCW (post-conception weeks) in Human fetal liver. (D) The expression proportion of ACE2/TMPRSS2 across different PCWs for the most expressed four cell types (early Erythroid, Fibroblast, Hepatocyte, Mid Erythroid) in Human fetal liver. (E) The expression ACE2 in Human fetal kidney. (F) The average expression level of ACE2/TMPRSS2 in Human lung at post-natal day 1 (PND1). AT1/AT2: alveolar type 1/2 cells.
Fig 3
Fig 3. The expression level of ACE2/TMPRSS2 in mouse fetal lung (E16.5, E18.5, PND1, PND3, PND7, PND10, PND15 and PND28).
(A) The dot plot of ACE2/TMPRSS2 in different time across different cell types. The point size represents the average level of ACE2/TMPRSS2 and the color scale means the -log(p.value). The expression level ACE2/TMPRSS2 for the point marked by green color is about 0.867. (B)The dot plot of ACE2 in different time across different cell types. The point size represents the average level of ACE2 and the color scale means the fold change. (C)The tSNE plots of cell type and feature plots of ACE2/TMPRSS2 in different times.
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Grants and funding

This work was supported by the Project funded by China Postdoctoral Science Foundation (XL) and was also supported by National Natural Science Foundation of China (81872673) (CX).