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.
journal_name
Cell Stem Celljournal_title
Cell stem cellauthors
Yang L,Han Y,Nilsson-Payant BE,Gupta V,Wang P,Duan X,Tang X,Zhu J,Zhao Z,Jaffré F,Zhang T,Kim TW,Harschnitz O,Redmond D,Houghton S,Liu C,Naji A,Ciceri G,Guttikonda S,Bram Y,Nguyen DT,Cioffi M,Chandar V,Hoagldoi
10.1016/j.stem.2020.06.015subject
Has Abstractpub_date
2020-07-02 00:00:00pages
125-136.e7issue
1eissn
1934-5909issn
1875-9777pii
S1934-5909(20)30282-4journal_volume
27pub_type
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