作者
Lay Teng Ang,Alana T Nguyen,Kevin J. Liu,Angela Chen,Xunhao Xiong,Matthew Curtis,Renata 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 Prescott,Kyle M. Loh
摘要
Stem cell research endeavors to generate specific subtypes of classically defined "cell types." Here, we generate >90% pure human artery or vein endothelial cells from pluripotent stem cells within 3-4 days. We specified artery cells by inhibiting vein-specifying signals and vice versa. These cells modeled viral infection of human vasculature by Nipah and Hendra viruses, which are extraordinarily deadly (∼57%-59% fatality rate) and require biosafety-level-4 containment. Generating pure populations of artery and vein cells highlighted that Nipah and Hendra viruses preferentially infected arteries; arteries expressed higher levels of their viral-entry receptor. Virally infected artery cells fused into syncytia containing up to 23 nuclei, which rapidly died. Despite infecting arteries and occupying ∼6%-17% of their transcriptome, Nipah and Hendra largely eluded innate immune detection, minimally eliciting interferon signaling. We thus efficiently generate artery and vein cells, introduce stem-cell-based toolkits for biosafety-level-4 virology, and explore the arterial tropism and cellular effects of Nipah and Hendra viruses.