Single-cell RNA expression profiling of SARS-CoV-2-related ACE2 and TMPRSS2 in human trophectoderm and placenta
Single-cell RNA expression profiling of SARS-CoV-2-related ACE2 and TMPRSS2 in human trophectoderm and placenta
复制标题
人滋养外胚层和胎盘中 SARS-CoV-2 相关 ACE2 和 TMPRSS2 的单细胞 RNA 表达谱
DOI：
10.1002/uog.22186
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发表时间：
2021-02-01
影响因子：
7.1
通讯作者：
Yang, H.
中科院分区：
文献类型：
--
作者：
Cui, D.;Liu, Y.;Yang, H.
目的研究严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）在人滋养外胚层（TE）和胎盘中的靶细胞特征和分布。我们使用SMART-Seq 2方法对4198个早期TE细胞、1260个早期妊娠胎盘细胞和189个来自24周胎盘（EVT_24W）的绒毛外滋养层细胞（EVT）进行了转录组学分析。此外，为了确认生物信息学结果，我们对本研究前瞻性招募的9名女性的3个早期妊娠、3个中期妊娠和3个晚期妊娠胎盘进行了免疫组织化学染色。结果通过生物信息学分析，我们鉴定了ACE 2和TMPRSS 2在人TE以及孕早期和孕中期胎盘中的表达。在人TE中，54.4%的TE 1细胞、9.0%的细胞滋养层细胞（CTB）、3.2%的EVT和29.5%的合体滋养层细胞（STB）呈ACE 2阳性。此外，90.7%的TE 1细胞、31.5%的CTB、22.1%的EVT和70.8%的STB为TMPRSS 2阳性。在胎盘细胞中，20.4%的CTB、44.1%的STB、3.4%的来自8周胎盘的EVT（EVT 8 W）和63%的EVT_24W是ACE 2阳性的，而1.6%的CTB、26.5%的STB、1.9%的EVT 8 W和20.1%的EVT_24W是TMPRSS 2阳性的。通路分析显示，ACE 2和TMPRSS 2均阳性的EVT_24 W细胞（ACE 2 + TMPRSS 2阳性）与分支结构的形态发生、细胞外基质相互作用、氧结合和抗氧化活性相关。ACE 2 + TMPRSS 2阳性TE 1细胞与病毒侵袭、上皮细胞增殖和细胞粘附能力的增加相关。结论ACE 2和TMPRSS 2阳性细胞存在于妊娠早期、中期和晚期的TE和胎盘中，提示SARS CoV 2可能通过胎盘传播并引起胎儿宫内感染。(C)2020年国际妇产科超声学会。
Objectives To examine the characteristics and distribution of possible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) target cells in the human trophectoderm (TE) and placenta.Methods Bioinformatics analysis was performed based on published single-cell transcriptomic datasets of early TE and first- and second-trimester human placentae. We conducted the transcriptomic analysis of 4198 early TE cells, 1260 first-trimester placental cells and 189 extra-villous trophoblast cells (EVTs) from 24-week placentae (EVT_24W) using the SMART-Seq2 method. In addition, to confirm the bioinformatic results, we performed immunohistochemical staining of three first-trimester, three second-trimester and three third-trimester placentae from nine women recruited prospectively to this study. We evaluated the expression of the SARS-CoV-2-related molecules angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2).Results Via bioinformatic analysis, we identified the existence of ACE2 and TMPRSS2 expression in human TE as well as in first- and second-trimester placentae. In the human TE, 54.4% of TE1 cells, 9.0% of cytotrophoblasts (CTBs), 3.2% of EVTs and 29.5% of syncytiotrophoblasts (STBs) were ACE2-positive. In addition, 90.7% of TE1 cells, 31.5% of CTBs, 22.1% of EVTs and 70.8% of STBs were TMPRSS2-positive. In placental cells, 20.4% of CTBs, 44.1% of STBs, 3.4% of EVTs from 8-week placentae (EVT 8W) and 63% of EVT_24W were ACE2-positive, while 1.6% of CTBs, 26.5% of STBs, 1.9% of EVT 8W and 20.1% of EVT_24W were TMPRSS2-positive. Pathway analysis revealed that EVT_24 W cells that were positive for both ACE2 and TMPRSS2 (ACE2 + TMPRSS2-positive) were associated with morphogenesis of branching structure, extracellular matrix interaction, oxygen binding and antioxidant activity. The ACE2 + TMPRSS2-positive TE1 cells were correlated with an increased capacity for viral invasion, epithelial-cell proliferation and cell adhesion. Expression of ACE2 and TMPRSS2 was observed on immunohistochemical staining in first-, second- and third-trimester placentae.Conclusions ACE2- and TMPRSS2-positive cells are present in the human TE and placenta in all three trimesters of pregnancy, which indicates the possibility that SARS-CoV-2 could spread via the placenta and cause intrauterine fetal infection. (C) 2020 International Society of Ultrasound in Obstetrics and Gynecology.