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

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.

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

“…Using a very permissive threshold of expression of one transcript per cell, only four cells with coexpression were detected in any of the three trimesters, resulting in an estimated < 1/10,000 cells. Our first-trimester data are in agreement with a prior report showing that there is minimal expression of ACE2 at the human maternal-fetal interface [62]; however, the same dataset was recently used to report the opposite [63]. Nonetheless, the co-expression of ACE2 and TMPRSS2 was not examined by either study.…”

Hypertension, Thrombosis, Kidney Failure, and Diabetes: Is COVID-19 an Endothelial Disease? A Comprehensive Evaluation of Clinical and Basic Evidence

“…To access host cells, SARS-CoV-2 uses a surface glycoprotein (peplomer) known as spike; ACE2 has been shown to be a co-receptor for coronavirus entry [28][29][30]. Therefore, the density of ACE2 in each tissue may correlate with the severity of the disease in that tissue [31][32][33][34][35][36]. Other receptors on the surface of human cells have been suggested to mediate the entry of SARS-CoV-2 [5], including transmembrane serine protease 2 (TMPRSS2) [37,38], sialic acid receptors [39,40], and extracellular matrix metalloproteinase inducer (CD147, also known as basigin) [41].…”

Atlas of ACE2 gene expression in mammals reveals novel insights in transmisson of SARS-Cov-2

“…SARS-CoV-2 and SARS-CoV are closely related, and both invade human cells via attaching their S proteins to a host transmembrane protein called angiotensin converting enzyme 2 (ACE2) as the entry point 3 . Using transcriptome data, some studies analyzed spatial expression patterns of ACE2 in various tissues and cell types of the human body, and reported that the receptor gene is indeed expressed in the lungs [4][5][6] . The connections between ACE2 expression and viral infection are further supported by cases from the United States, which confirmed for the first time the presence of SARS-CoV-2 in both the upper respiratory tract and stool sample of COVID-19 patients 7 .…”