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Generating human artery and vein cells from pluripotent stem cells highlights the arterial tropism of Nipah and Hendra viruses.
Ang, Lay Teng; Nguyen, Alana T; Liu, Kevin J; Chen, Angela; Xiong, Xiaochen; Curtis, Matthew; Martin, Renata M; Raftry, Brian C; Ng, Chun Yi; Vogel, Uwe; Lander, Angelika; Lesch, Benjamin J; Fowler, Jonas L; Holman, Alyssa R; Chai, Timothy; Vijayakumar, Siva; Suchy, Fabian P; Nishimura, Toshinobu; Bhadury, Joydeep; Porteus, Matthew H; Nakauchi, Hiromitsu; Cheung, Christine; George, Steven C; Red-Horse, Kristy; Prescott, Joseph B; Loh, Kyle M.
Affiliation
  • Ang LT; Stanford Institute for Stem Cell Biology & Regenerative Medicine, Stanford University, Stanford, CA 94305, USA. Electronic address: layteng@stanford.edu.
  • Nguyen AT; Stanford Institute for Stem Cell Biology & Regenerative Medicine, Stanford University, Stanford, CA 94305, USA; Department of Developmental Biology, Stanford Cardiovascular Institute, Stanford University, Stanford, CA 94305, USA.
  • Liu KJ; Stanford Institute for Stem Cell Biology & Regenerative Medicine, Stanford University, Stanford, CA 94305, USA.
  • Chen A; Stanford Institute for Stem Cell Biology & Regenerative Medicine, Stanford University, Stanford, CA 94305, USA; Department of Developmental Biology, Stanford Cardiovascular Institute, Stanford University, Stanford, CA 94305, USA.
  • Xiong X; Stanford Institute for Stem Cell Biology & Regenerative Medicine, Stanford University, Stanford, CA 94305, USA; Department of Developmental Biology, Stanford Cardiovascular Institute, Stanford University, Stanford, CA 94305, USA.
  • Curtis M; Department of Biomedical Engineering, University of California, Davis, Davis, CA 95616, USA.
  • Martin RM; Stanford Institute for Stem Cell Biology & Regenerative Medicine, Stanford University, Stanford, CA 94305, USA; Department of Pediatrics, Stanford University, Stanford, CA 94305, USA.
  • Raftry BC; Stanford Institute for Stem Cell Biology & Regenerative Medicine, Stanford University, Stanford, CA 94305, USA; Department of Biology, Stanford University, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
  • Ng CY; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore.
  • Vogel U; Center for Biological Threats and Special Pathogens, Robert Koch Institute, Berlin 13353, Germany.
  • Lander A; Center for Biological Threats and Special Pathogens, Robert Koch Institute, Berlin 13353, Germany.
  • Lesch BJ; Stanford Institute for Stem Cell Biology & Regenerative Medicine, Stanford University, Stanford, CA 94305, USA; Department of Pediatrics, Stanford University, Stanford, CA 94305, USA.
  • Fowler JL; Stanford Institute for Stem Cell Biology & Regenerative Medicine, Stanford University, Stanford, CA 94305, USA; Department of Developmental Biology, Stanford Cardiovascular Institute, Stanford University, Stanford, CA 94305, USA.
  • Holman AR; Stanford Institute for Stem Cell Biology & Regenerative Medicine, Stanford University, Stanford, CA 94305, USA; Department of Developmental Biology, Stanford Cardiovascular Institute, Stanford University, Stanford, CA 94305, USA.
  • Chai T; Stanford Institute for Stem Cell Biology & Regenerative Medicine, Stanford University, Stanford, CA 94305, USA; Department of Developmental Biology, Stanford Cardiovascular Institute, Stanford University, Stanford, CA 94305, USA.
  • Vijayakumar S; Stanford Institute for Stem Cell Biology & Regenerative Medicine, Stanford University, Stanford, CA 94305, USA; Department of Developmental Biology, Stanford Cardiovascular Institute, Stanford University, Stanford, CA 94305, USA.
  • Suchy FP; Stanford Institute for Stem Cell Biology & Regenerative Medicine, Stanford University, Stanford, CA 94305, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
  • Nishimura T; Stanford Institute for Stem Cell Biology & Regenerative Medicine, Stanford University, Stanford, CA 94305, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
  • Bhadury J; Stanford Institute for Stem Cell Biology & Regenerative Medicine, Stanford University, Stanford, CA 94305, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
  • Porteus MH; Stanford Institute for Stem Cell Biology & Regenerative Medicine, Stanford University, Stanford, CA 94305, USA; Department of Pediatrics, Stanford University, Stanford, CA 94305, USA.
  • Nakauchi H; Stanford Institute for Stem Cell Biology & Regenerative Medicine, Stanford University, Stanford, CA 94305, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
  • Cheung C; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore; Institute of Molecular and Cell Biology, A(∗)STAR, Singapore 138673, Singapore.
  • George SC; Department of Biomedical Engineering, University of California, Davis, Davis, CA 95616, USA.
  • Red-Horse K; Stanford Institute for Stem Cell Biology & Regenerative Medicine, Stanford University, Stanford, CA 94305, USA; Department of Biology, Stanford University, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
  • Prescott JB; Center for Biological Threats and Special Pathogens, Robert Koch Institute, Berlin 13353, Germany. Electronic address: prescottj@rki.de.
  • Loh KM; Stanford Institute for Stem Cell Biology & Regenerative Medicine, Stanford University, Stanford, CA 94305, USA; Department of Developmental Biology, Stanford Cardiovascular Institute, Stanford University, Stanford, CA 94305, USA. Electronic address: kyleloh@stanford.edu.
Cell ; 185(14): 2523-2541.e30, 2022 07 07.
Article in En | MEDLINE | ID: mdl-35738284
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 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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Pluripotent Stem Cells / Hendra Virus / Nipah Virus Limits: Humans Language: En Journal: Cell Year: 2022 Document type: Article
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Pluripotent Stem Cells / Hendra Virus / Nipah Virus Limits: Humans Language: En Journal: Cell Year: 2022 Document type: Article