Novel Targets of SARS-CoV-2 Spike Protein in Human Fetal Brain Development Suggest Early Pregnancy Vulnerability.
Novel Targets of SARS-CoV-2 Spike Protein in Human Fetal Brain Development Suggest Early Pregnancy Vulnerability.
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SARS-COV-2峰值蛋白在人类胎儿脑发育中的新靶标表明妊娠脆弱性。
DOI：
10.3389/fnins.2020.614680
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发表时间：
2020
影响因子：
4.3
通讯作者：
Hsieh J
中科院分区：
文献类型：
--
作者：
Varma P;Lybrand ZR;Antopia MC;Hsieh J
孕妇感染严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的风险更大，因为她们的免疫力改变和心血管系统紧张。对胎盘、胚胎和大脑类器官的新研究表明，包括大脑在内的胎儿器官也可能容易受到2019冠状病毒病（COVID-19）的影响。此外，来自巴黎的一项病例研究报告了孕妇所生新生儿的一过性神经系统并发症。然而，胎儿脑是否表达与冠状病毒刺突蛋白（S）相互作用的细胞组分仍然知之甚少，刺突蛋白（S）促进病毒和宿主细胞膜的融合，并且是病毒进入的主要蛋白。为了解决这个问题，我们分析了已知的（ACE 2，TMPRSS 2和FURIN）和新的（ZDHHC 5，GOLGA 7和ATP 1A 1）S蛋白相互作用物在公开可用的胎脑体积和单细胞RNA测序数据集中的表达。跨越受孕后8周（wpc）-37wpc的胎儿大脑多个区域的批量RNA测序分析表明，两种已知的S蛋白相互作用物以低水平表达，中位数标准化基因表达值范围为0.08 - 0.06（ACE 2）和0.01-0.02（TMPRSS 2）。然而，第三个已知的S蛋白相互作用物FURIN在胎儿脑中高度表达（11.1-44.09）。有趣的是，所有三种新的S蛋白相互作用物在整个胎儿脑发育中大量表达，标准化基因表达中值范围为20.38-21.60（ZDHHC 5）、92.47-68.35（GOLGA 7）和65.45-194.5（ATP 1A 1）。此外，新型相互作用物的表达峰值在12- 26 wpc左右。使用公开可用的单细胞RNA测序数据集，我们进一步表明，新的S蛋白相互作用物与神经元的共表达高于与神经祖细胞和星形胶质细胞的共表达。这些结果表明，即使两个已知的S蛋白相互作用物在胎儿大脑中以低水平存在，新的S蛋白相互作用物大量存在，并可能在SARS-CoV-2胎儿大脑发病机制中发挥直接或间接的作用，特别是在妊娠的第2和第3个三个月。
Pregnant women are at greater risk of infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), because of their altered immunity and strained cardiovascular system. Emerging studies of placenta, embryos, and cerebral organoids suggest that fetal organs including brain could also be vulnerable to coronavirus disease 2019 (COVID-19). Additionally, a case study from Paris has reported transient neurological complications in neonates born to pregnant mothers. However, it remains poorly understood whether the fetal brain expresses cellular components that interact with Spike protein (S) of coronaviruses, which facilitates fusion of virus and host cell membrane and is the primary protein in viral entry. To address this question, we analyzed the expression of known (ACE2, TMPRSS2, and FURIN) and novel (ZDHHC5, GOLGA7, and ATP1A1) S protein interactors in publicly available fetal brain bulk and single cell RNA sequencing datasets. Bulk RNA sequencing analysis across multiple regions of fetal brain spanning 8 weeks post conception (wpc)−37wpc indicates that two of the known S protein interactors are expressed at low levels with median normalized gene expression values ranging from 0.08 to 0.06 (ACE2) and 0.01–0.02 (TMPRSS2). However, the third known S protein interactor FURIN is highly expressed (11.1–44.09) in fetal brain. Interestingly, all three novel S protein interactors are abundantly expressed throughout fetal brain development with median normalized gene expression values ranging from 20.38–21.60 (ZDHHC5), 92.47–68.35 (GOLGA7), and 65.45–194.5 (ATP1A1). Moreover, the peaks of expression of novel interactors is around 12–26wpc. Using publicly available single cell RNA sequencing datasets, we further show that novel S protein interactors show higher co-expression with neurons than with neural progenitors and astrocytes. These results suggest that even though two of the known S protein interactors are present at low levels in fetal brain, novel S protein interactors are abundantly present and could play a direct or indirect role in SARS-CoV-2 fetal brain pathogenesis, especially during the 2nd and 3rd trimesters of pregnancy.
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DOI：
10.1073/pnas.1507125112
发表时间：
2015-06-09
影响因子：
11.1
作者：
Darmanis S;Sloan SA;Zhang Y;Enge M;Caneda C;Shuer LM;Hayden Gephart MG;Barres BA;Quake SR
通讯作者：
Quake SR
影响因子：
56.9
作者：
Cai, Yongfei;Zhang, Jun;Chen, Bing
通讯作者：
Chen, Bing
影响因子：
5.4
作者：
Burkard, Christine;Verheije, Monique H.;de Haan, Cornelis A. M.
通讯作者：
de Haan, Cornelis A. M.
影响因子：
7.3
作者：
Hamming, I;Timens, W;van Goor, H
通讯作者：
van Goor, H
影响因子：
64.8
作者：
Gordon, David E.;Jang, Gwendolyn M.;Krogan, Nevan J.
通讯作者：
Krogan, Nevan J.