Dataset Information

SARS-CoV-2 Targets by the pscRNA Profiling of ACE2, TMPRSS2 and Furin Proteases.

ABSTRACT: The cellular targets of SARS-CoV-2, the novel coronavirus causing the COVID-19 pandemic, is still rudimentary. Here, we incorporated the protein information to analyze the expression of ACE2, the SARS-CoV-2 receptor, together with co-factors, TMPRSS2 and Furin, at single-cell level in situ, which we called protein-proofed single-cell RNA (pscRNA) profiling. Systemic analysis across 36 tissues revealed a rank list of candidate cells potentially vulnerable to SARS-CoV-2. The top targets are lung AT2 cells and macrophages, then cardiomyocytes and adrenal gland stromal cells, followed by stromal cells in testis, ovary, and thyroid, whereas the kidney proximal tubule cells, cholangiocytes, and enterocytes are less likely to be the primary SARS-CoV-2 targets. Actually, the stomach may constitute a physical barrier against SARS-CoV-2 as the acidic environment (pH < 2.0) could completely inactivate SARS-CoV-2 pseudo-viruses. Together, we provide a comprehensive view on the potential SARS-CoV-2 targets by pscRNA profiling.

SUBMITTER: Zhou L

PROVIDER: S-EPMC7591870 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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SARS-CoV-2 Targets by the pscRNA Profiling of ACE2, TMPRSS2 and Furin Proteases.

Zhou Lulin L Niu Zubiao Z Jiang Xiaoyi X Zhang Zhengrong Z Zheng You Y Wang Zhongyi Z Zhu Yichao Y Gao Lihua L Huang Hongyan H Wang Xiaoning X Sun Qiang Q

iScience 20201028 11

The cellular targets of SARS-CoV-2, the novel coronavirus causing the COVID-19 pandemic, is still rudimentary. Here, we incorporated the protein information to analyze the expression of ACE2, the SARS-CoV-2 receptor, together with co-factors, TMPRSS2 and Furin, at single-cell level <i>in situ</i>, which we called protein-proofed single-cell RNA (pscRNA) profiling. Systemic analysis across 36 tissues revealed a rank list of candidate cells potentially vulnerable to SARS-CoV-2. The top targets are ...[more]

PMID: 33134888

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Project description:The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has had a massive impact on human lives worldwide. While the airborne SARS-CoV-2 primarily affects the lungs, viremia is not uncommon. As placental trophoblasts are directly bathed in maternal blood, they are vulnerable to SARS-CoV-2. Intriguingly, the human fetus is largely spared from SARS-CoV-2 infection. We tested whether the human placenta expresses the main SARS-CoV-2 entry factors angiotensin-converting enzyme 2 (ACE2), transmembrane protease serine 2 (TMPRSS2), and furin and showed that ACE2 and TMPRSS2 are expressed in the trophoblast rather than in other placental villous cells. While furin is expressed in the main placental villous cell types, we surveyed, trophoblasts exhibit the highest expression. In line with the expression of these entry factors, we demonstrated that a SARS-CoV-2 pseudovirus could enter primary human trophoblasts. Mechanisms underlying placental defense against SARS-CoV-2 infection likely involve postentry processing, which may be germane for mitigating interventions against SARS-CoV-2.IMPORTANCE Pregnant women worldwide have been affected by COVID-19. As the virus is commonly spread to various organs via the bloodstream and because human placental trophoblasts are directly bathed in maternal blood, feto-placental infection by SARS-CoV-2 seems likely. However, despite the heightened risk to pregnant women, thus far the transmission risk of COVID-19 to the feto-placental unit seems extremely low. This has been recently attributed to a negligible expression of SARS-CoV-2 entry factors in the human placenta. We therefore sought to explore the expression of the entry factors ACE2 and TMPRSS2 in the different cell types of human placental villi. Using a combination of transcriptome sequencing (RNA-seq), real-time quantitative PCR (RT-qPCR), in situ hybridization, and immunofluorescence, we found that trophoblasts, but not the other main villous cell types, express ACE2 and TMPRSS2, with a broad expression of furin. Correspondingly, we also showed that primary human trophoblasts are permissive to entry of SARS-CoV-2 pseudovirus particles.

Dataset Information

SARS-CoV-2 Targets by the pscRNA Profiling of ACE2, TMPRSS2 and Furin Proteases.

Publications

SARS-CoV-2 Targets by the pscRNA Profiling of ACE2, TMPRSS2 and Furin Proteases.

Similar Datasets

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