2. Academic Validation
  3. A Human Pluripotent Stem Cell-based Platform to Study SARS-CoV-2 Tropism and Model Virus Infection in Human Cells and Organoids

A Human Pluripotent Stem Cell-based Platform to Study SARS-CoV-2 Tropism and Model Virus Infection in Human Cells and Organoids

  • Cell Stem Cell. 2020 Jul 2;27(1):125-136.e7. doi: 10.1016/j.stem.2020.06.015.
Liuliu Yang 1,  Yuling Han 1,  Benjamin E Nilsson-Payant 2,  Vikas Gupta 3,  Pengfei Wang 4,  Xiaohua Duan 5,  Xuming Tang 1,  Jiajun Zhu 1,  Zeping Zhao 1,  Fabrice Jaffré 1,  Tuo Zhang 6,  Tae Wan Kim 7,  Oliver Harschnitz 7,  David Redmond 8,  Sean Houghton 8,  Chengyang Liu 9,  Ali Naji 9,  Gabriele Ciceri 7,  Sudha Guttikonda 10,  Yaron Bram 3,  Duc-Huy T Nguyen 3,  Michele Cioffi 11,  Vasuretha Chandar 3,  Daisy A Hoagland 2,  Yaoxing Huang 4,  Jenny Xiang 6,  Hui Wang 12,  David Lyden 11,  Alain Borczuk 13,  Huanhuan Joyce Chen 14,  Lorenz Studer 7,  Fong Cheng Pan 15,  David D Ho 16,  Benjamin R tenOever 17,  Todd Evans 18,  Robert E Schwartz 19,  Shuibing Chen 20
Affiliations

Affiliations

  • 1 Department of Surgery, Weill Cornell Medicine, 1300 York Ave, New York, NY 10065, USA.
  • 2 Department of Microbiology, Icahn School of Medicine at Mount Sinai. 1468 Madison Ave. New York, NY 10029, USA.
  • 3 Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine, 1300 York Ave, New York, NY 10065, USA.
  • 4 Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA.
  • 5 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.
  • 6 Genomic Resource Core Facility, Weill Cornell Medicine, New York, NY 10065, USA.
  • 7 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.
  • 8 Division of Regenerative Medicine, Ansary Stem Cell Institute, Weill Cornell Medicine, New York, NY 10065, USA.
  • 9 Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
  • 10 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, USA.
  • 11 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.
  • 12 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.
  • 13 Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, USA.
  • 14 The Pritzker School of Molecular Engineering, the Ben May Department for Cancer Research, the University of Chicago, IL, USA.
  • 15 Department of Surgery, Weill Cornell Medicine, 1300 York Ave, New York, NY 10065, USA. Electronic address: fcp2002@med.cornell.edu.
  • 16 Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA. Electronic address: dh2994@cumc.columbia.edu.
  • 17 Department of Microbiology, Icahn School of Medicine at Mount Sinai. 1468 Madison Ave. New York, NY 10029, USA. Electronic address: benjamin.tenoever@mssm.edu.
  • 18 Department of Surgery, Weill Cornell Medicine, 1300 York Ave, New York, NY 10065, USA. Electronic address: tre2003@med.cornell.edu.
  • 19 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.
  • 20 Department of Surgery, Weill Cornell Medicine, 1300 York Ave, New York, NY 10065, USA. Electronic address: shc2034@med.cornell.edu.
PMID: 32579880 DOI: 10.1016/j.stem.2020.06.015
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.

Keywords

SARS-CoV-2; alpha cells; beta cells; human pluripotent stem cells; liver organoids; pancreatic endocrine cells.

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