Single-cell RNA expression profiling of ACE2 and AXL in the human maternal–Fetal interface

2019 novel coronavirus disease has resulted in thousands of critically ill patients in China, which is a serious threat to people's life and health. Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) was reported to share the same receptor, angiotensin-converting enzyme 2 (ACE2), with SARS-CoV. Here, based on the public single-cell RNA-sequencing database, we analyzed the mRNA expression profile of putative receptor ACE2 and AXL receptor tyrosine kinase (AXL) in the early maternal-fetal interface. The result indicates that the ACE2 has very low expression in the different cell types of early maternal-fetal interface, except slightly high in decidual perivascular cells cluster 1 (PV1). Interestingly, we found that the Zika virus (ZIKV) receptor AXL expression is concentrated in perivascular cells and stromal cells, indicating that there are relatively more AXL-expressing cells in the early maternal-fetal interface. This study provides a possible infection route and mechanism for the SARS-CoV-2- or ZIKV-infected mother-to-fetus transmission disease, which could be informative for future therapeutic strategy development. Zheng Qing-Liang 1 Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 201204 Duan Tao 2 Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 201204 Jin Li-Ping 3 Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 201204 Wang W, Tang J, Wei F. Updated understanding of the outbreak of 2019 novel coronavirus (2019-nCoV) in Wuhan, China. J Med Virol 2020. [Ahead of print]. doi: 10.1002/jmv.25689. Chen H, Guo J, Wang C, Luo F, Yu X, Zhang W, et al. Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: A retrospective review of medical records. Lancet 2020. [Ahead of print]. doi: 10.1016/S0140-6736(20) 30360-3. Xu X, Chen P, Wang J, Feng J, Zhou H, Li X, et al. Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission. Sci China Life Sci 2020. [Ahead of print]. doi: 10.1007/s11427-020-1637-5. Li W, Sui J, Huang IC, Kuhn JH, Radoshitzky SR, Marasco WA, et al. The S proteins of human coronavirus NL63 and severe acute respiratory syndrome coronavirus bind overlapping regions of ACE2. Virology 2007;367:367-74. doi: 10.1016/j.virol.2007.04.035. Ferreira LM, Meissner TB, Tilburgs T, Strominger JL. HLA-G: At the interface of maternal-fetal tolerance. Trends Immunol 2017;38:272-86. doi: 10.1016/j.it.2017.01.009. Picelli S, Faridani OR, Bjorklund AK, Winberg G, Sagasser S, Sandberg R. Full-length RNA-seq from single cells using Smart-seq2. Nat Protoc 2014;9:171-81. doi: 10.1038/nprot.2014.006. Vento-Tormo R, Efremova M, Botting RA, Turco MY, Vento-Tormo M, Meyer KB, et al. Single-cell reconstruction of the early maternal-fetal interface in humans. Nature 2018;563:347-53. doi: 10.1038/s41586-018-0698-6. Zhao Y, Zhao Z, Wang Y, Zhou Y, Ma Y, Zuo W. Single-cell RNA expression profiling of ACE2, the putative receptor of Wuhan 2019-nCov. BioRxiv 2020. [Ahead of print]. doi: 10.1101/2020.01.26.919985. Lazear HM, Diamond MS. Zika virus: New clinical syndromes and its emergence in the western hemisphere. J Virol 2016;90:4864-75. doi: 10.1128/JVI.00252-16. Petersen LR, Jamieson DJ, Powers AM, Honein MA. Zika virus. N Engl J Med 2016;374:1552-63. doi: 10.1056/NEJMra1602113. Rasmussen SA, Jamieson DJ, Honein MA, Petersen LR. Zika virus and birth defects - Reviewing the evidence for causality. N Engl J Med 2016;374:1981-7. doi: 10.1056/NEJMsr1604338. Brasil P, Pereira JP Jr., Moreira ME, Ribeiro Nogueira RM, Damasceno L, Wakimoto M, et al. Zika virus infection in pregnant women in Rio de Janeiro. N Engl J Med 2016;375:2321-34. doi: 10.1056/NEJMoa1602412. Tabata T, Petitt M, Puerta-Guardo H, Michlmayr D, Wang C, Fang-Hoover J, et al. Zika virus targets different primary human placental cells, suggesting two routes for vertical transmission. Cell Host Microbe 2016;20:155-66. doi: 10.1016/j.chom.2016.07.002. Quicke KM, Bowen JR, Johnson EL, McDonald CE, Ma H, O'Neal JT, et al. Zika virus Infects Human Placental Macrophages. Cell Host Microbe 2016;20:83-90. doi: 10.1016/j.chom.2016.05.015.