A human pluripotent stem cell-based platform to study SARS-CoV-2 tropism and model virus infection in human cells and organoids Journal Article


Authors: Yang, L.; Han, Y.; Nilsson-Payant, B. E.; Gupta, V.; Wang, P.; Duan, X.; Tang, X.; Zhu, J.; Zhao, Z.; Jaffré, F.; Zhang, T.; Kim, T. W.; Harschnitz, O.; Redmond, D.; Houghton, S.; Liu, C.; Naji, A.; Ciceri, G.; Guttikonda, S.; Bram, Y.; Nguyen, D. H. T.; Cioffi, M.; Chandar, V.; Hoagland, D. A.; Huang, Y.; Xiang, J.; Wang, H.; Lyden, D.; Borczuk, A.; Chen, H. J.; Studer, L.; Pan, F. C.; Ho, D. D.; tenOever, B. R.; Evans, T.; Schwartz, R. E.; Chen, S.
Article Title: A human pluripotent stem cell-based platform to study SARS-CoV-2 tropism and model virus infection in human cells and organoids
Abstract: Yang et al. show that hPSC-derived cells and organoids provide valuable models to study SARS-CoV-2 tropism and to model COVID-19. They find that hPSC-derived pancreatic endocrine cells and human adult hepatocyte and cholangiocyte organoids are permissive to SARS-CoV-2 infection. © 2020 Elsevier Inc. 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. © 2020 Elsevier Inc.
Keywords: pancreas; mouse; animal; metabolism; animals; mice; hepatocytes; biological model; models, biological; cell line; pathology; physiology; virology; liver; liver cell; autopsy; virus pneumonia; induced pluripotent stem cells; tropism; virus entry; pandemic; beta cells; dipeptidyl carboxypeptidase; virus internalization; human pluripotent stem cells; pneumonia, viral; induced pluripotent stem cell; humans; human; coronavirus infections; organoids; peptidyl-dipeptidase a; organoid; betacoronavirus; coronavirus infection; pandemics; angiotensin converting enzyme 2; sars-cov-2; alpha cells; liver organoids; pancreatic endocrine cells
Journal Title: Cell Stem Cell
Volume: 27
Issue: 1
ISSN: 1934-5909
Publisher: Cell Press  
Date Published: 2020-07-02
Start Page: 125
End Page: 136.e7
Language: English
DOI: 10.1016/j.stem.2020.06.015
PUBMED: 32579880
PROVIDER: scopus
PMCID: PMC7303620
DOI/URL:
Notes: Article -- Export Date: 1 September 2020 -- Source: Scopus
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MSK Authors
  1. Lorenz Studer
    182 Studer
  2. Taewan Kim
    7 Kim
  3. Gabriele Ciceri
    5 Ciceri