美国斯坦福大学Kyle M. Loh研究组揭示，从多能干细胞生成人类动脉和静脉细胞突出了尼帕病毒和亨德拉病毒的动脉嗜性。该项研究成果发表在2022年6月22日出版的《细胞》上。
他们在 3-4 天内从多能干细胞中生成 >90% 的纯人类动脉或静脉内皮细胞。他们通过抑制静脉特异性信号来指定动脉细胞，反之亦然。这些细胞模拟了尼帕病毒和亨德拉病毒对人体脉管系统的病毒感染，这些病毒非常致命（～57%–59% 的致死率）并且需要 4 级生物安全防护。产生纯的动脉和静脉细胞群突显了尼帕病毒和亨德拉病毒优先感染动脉；动脉表达了更高水平的病毒进入受体。
病毒感染的动脉细胞融合成含有多达 23 个细胞核的合胞体，然后迅速死亡。尽管感染了动脉并占据了约 6%–17% 的转录组，尼帕病毒和亨德拉病毒很大程度上避开了先天免疫检测，最小程度地引发干扰素信号传导。因此，他们有效地生成了动脉和静脉细胞，引入了基于干细胞的工具包用于生物安全 4 级病毒学，并探索尼帕病毒和亨德拉病毒的动脉嗜性和细胞效应。
附：英文原文
Title: Generating human artery and vein cells from pluripotent stem cells highlights the arterial tropism of Nipah and Hendra viruses
Author: Lay Teng Ang, Alana T. Nguyen, Kevin J. Liu, Angela Chen, Xiaochen Xiong, Matthew Curtis, Renata M. Martin, Brian C. Raftry, Chun Yi Ng, Uwe Vogel, Angelika Lander, Benjamin J. Lesch, Jonas L. Fowler, Alyssa R. Holman, Timothy Chai, Siva Vijayakumar, Fabian P. Suchy, Toshinobu Nishimura, Joydeep Bhadury, Matthew H. Porteus, Hiromitsu Nakauchi, Christine Cheung, Steven C. George, Kristy Red-Horse, Joseph B. Prescott, Kyle M. Loh
Issue&Volume: 2022-06-22
Abstract: Stem cell research endeavors to generate specific subtypes of classically defined“cell types.” Here, we generate >90% pure human artery or vein endothelial cells frompluripotent stem cells within 3–4 days. We specified artery cells by inhibiting vein-specifyingsignals and vice versa. These cells modeled viral infection of human vasculature byNipah and Hendra viruses, which are extraordinarily deadly (～57%–59% fatality rate)and require biosafety-level-4 containment. Generating pure populations of artery andvein cells highlighted that Nipah and Hendra viruses preferentially infected arteries;arteries expressed higher levels of their viral-entry receptor. Virally infected arterycells fused into syncytia containing up to 23 nuclei, which rapidly died. Despiteinfecting arteries and occupying ～6%–17% of their transcriptome, Nipah and Hendralargely eluded innate immune detection, minimally eliciting interferon signaling.We thus efficiently generate artery and vein cells, introduce stem-cell-based toolkitsfor biosafety-level-4 virology, and explore the arterial tropism and cellular effectsof Nipah and Hendra viruses.
DOI: 10.1016/j.cell.2022.05.024
Source: https://www.cell.com/cell/fulltext/S0092-8674(22)00655-9