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A Human Pluripotent Stem Cell-based Platform to Study SARS-CoV-2 Tropism and Model Virus Infection in Human Cells and Organoids.
Yang, Liuliu; Han, Yuling; Nilsson-Payant, Benjamin E; Gupta, Vikas; Wang, Pengfei; Duan, Xiaohua; Tang, Xuming; Zhu, Jiajun; Zhao, Zeping; Jaffré, Fabrice; Zhang, Tuo; Kim, Tae Wan; Harschnitz, Oliver; Redmond, David; Houghton, Sean; Liu, Chengyang; Naji, Ali; Ciceri, Gabriele; Guttikonda, Sudha; Bram, Yaron; Nguyen, Duc-Huy T; Cioffi, Michele; Chandar, Vasuretha; Hoagland, Daisy A; Huang, Yaoxing; Xiang, Jenny; Wang, Hui; Lyden, David; Borczuk, Alain; Chen, Huanhuan Joyce; Studer, Lorenz; Pan, Fong Cheng; Ho, David D; tenOever, Benjamin R; Evans, Todd; Schwartz, Robert E; Chen, Shuibing.
  • Yang L; Department of Surgery, Weill Cornell Medicine, 1300 York Ave, New York, NY 10065, USA.
  • Han Y; Department of Surgery, Weill Cornell Medicine, 1300 York Ave, New York, NY 10065, USA.
  • Nilsson-Payant BE; Department of Microbiology, Icahn School of Medicine at Mount Sinai. 1468 Madison Ave. New York, NY 10029, USA.
  • Gupta V; Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine, 1300 York Ave, New York, NY 10065, USA.
  • Wang P; Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA.
  • Duan X; Department of Surgery, Weill Cornell Medicine, 1300 York Ave, New York, NY 10065, USA; School of Life Science and Technology, ShanghaiTech University, 201210 Shanghai, China.
  • Tang X; Department of Surgery, Weill Cornell Medicine, 1300 York Ave, New York, NY 10065, USA.
  • Zhu J; Department of Surgery, Weill Cornell Medicine, 1300 York Ave, New York, NY 10065, USA.
  • Zhao Z; Department of Surgery, Weill Cornell Medicine, 1300 York Ave, New York, NY 10065, USA.
  • Jaffré F; Department of Surgery, Weill Cornell Medicine, 1300 York Ave, New York, NY 10065, USA.
  • Zhang T; Genomic Resource Core Facility, Weill Cornell Medicine, New York, NY 10065, USA.
  • Kim TW; The Center for Stem Cell Biology, Sloan Kettering Institute for Cancer Research, New York, NY 10065, USA; Developmental Biology Program, Sloan Kettering Institute for Cancer Research, New York, NY 10065, USA.
  • Harschnitz O; The Center for Stem Cell Biology, Sloan Kettering Institute for Cancer Research, New York, NY 10065, USA; Developmental Biology Program, Sloan Kettering Institute for Cancer Research, New York, NY 10065, USA.
  • Redmond D; Division of Regenerative Medicine, Ansary Stem Cell Institute, Weill Cornell Medicine, New York, NY 10065, USA.
  • Houghton S; Division of Regenerative Medicine, Ansary Stem Cell Institute, Weill Cornell Medicine, New York, NY 10065, USA.
  • Liu C; Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
  • Naji A; Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
  • Ciceri G; The Center for Stem Cell Biology, Sloan Kettering Institute for Cancer Research, New York, NY 10065, USA; Developmental Biology Program, Sloan Kettering Institute for Cancer Research, New York, NY 10065, USA.
  • Guttikonda S; The Center for Stem Cell Biology, Sloan Kettering Institute for Cancer Research, New York, NY 10065, USA; Developmental Biology Program, Sloan Kettering Institute for Cancer Research, New York, NY 10065, USA; Weill Cornell/Rockefeller/Sloan Kettering Tri-Institutional MD-PhD Program, New York, NY, U
  • Bram Y; Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine, 1300 York Ave, New York, NY 10065, USA.
  • Nguyen DT; Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine, 1300 York Ave, New York, NY 10065, USA.
  • Cioffi M; Children's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.
  • Chandar V; Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine, 1300 York Ave, New York, NY 10065, USA.
  • Hoagland DA; Department of Microbiology, Icahn School of Medicine at Mount Sinai. 1468 Madison Ave. New York, NY 10029, USA.
  • Huang Y; Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA.
  • Xiang J; Genomic Resource Core Facility, Weill Cornell Medicine, New York, NY 10065, USA.
  • Wang H; School of Life Science and Technology, ShanghaiTech University, 201210 Shanghai, China; State Key Laboratory of Oncogenes and Related Genes, Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
  • Lyden D; Children's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.
  • Borczuk A; Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, USA.
  • Chen HJ; The Pritzker School of Molecular Engineering, the Ben May Department for Cancer Research, the University of Chicago, IL, USA.
  • Studer L; The Center for Stem Cell Biology, Sloan Kettering Institute for Cancer Research, New York, NY 10065, USA; Developmental Biology Program, Sloan Kettering Institute for Cancer Research, New York, NY 10065, USA.
  • Pan FC; Department of Surgery, Weill Cornell Medicine, 1300 York Ave, New York, NY 10065, USA. Electronic address: fcp2002@med.cornell.edu.
  • Ho DD; Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA. Electronic address: dh2994@cumc.columbia.edu.
  • tenOever BR; Department of Microbiology, Icahn School of Medicine at Mount Sinai. 1468 Madison Ave. New York, NY 10029, USA. Electronic address: benjamin.tenoever@mssm.edu.
  • Evans T; Department of Surgery, Weill Cornell Medicine, 1300 York Ave, New York, NY 10065, USA. Electronic address: tre2003@med.cornell.edu.
  • Schwartz RE; Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine, 1300 York Ave, New York, NY 10065, USA; Department of Physiology, Biophysics and Systems Biology, Weill Cornell Medicine, 1300 York Ave, New York, NY 10065, USA. Electronic address: res2025@med.cornell.edu.
  • Chen S; Department of Surgery, Weill Cornell Medicine, 1300 York Ave, New York, NY 10065, USA. Electronic address: shc2034@med.cornell.edu.
Cell Stem Cell ; 27(1): 125-136.e7, 2020 07 02.
Article in English | MEDLINE | ID: covidwho-610467
ABSTRACT
SARS-CoV-2 has caused the COVID-19 pandemic. There is an urgent need for physiological models to study SARS-CoV-2 infection using human disease-relevant cells. COVID-19 pathophysiology includes respiratory failure but involves other organ systems including gut, liver, heart, and pancreas. We present an experimental platform comprised of cell and organoid derivatives from human pluripotent stem cells (hPSCs). A Spike-enabled pseudo-entry virus infects pancreatic endocrine cells, liver organoids, cardiomyocytes, and dopaminergic neurons. Recent clinical studies show a strong association with COVID-19 and diabetes. We find that human pancreatic beta cells and liver organoids are highly permissive to SARS-CoV-2 infection, further validated using adult primary human islets and adult hepatocyte and cholangiocyte organoids. SARS-CoV-2 infection caused striking expression of chemokines, as also seen in primary human COVID-19 pulmonary autopsy samples. hPSC-derived cells/organoids provide valuable models for understanding the cellular responses of human tissues to SARS-CoV-2 infection and for disease modeling of COVID-19.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / Organoids / Coronavirus Infections / Tropism / Induced Pluripotent Stem Cells / Betacoronavirus / Models, Biological Type of study: Prognostic study Limits: Animals / Humans Language: English Journal: Cell Stem Cell Year: 2020 Document Type: Article Affiliation country: J.stem.2020.06.015

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / Organoids / Coronavirus Infections / Tropism / Induced Pluripotent Stem Cells / Betacoronavirus / Models, Biological Type of study: Prognostic study Limits: Animals / Humans Language: English Journal: Cell Stem Cell Year: 2020 Document Type: Article Affiliation country: J.stem.2020.06.015