SARS-CoV-2 infection of human pluripotent stem cell-derived liver organoids reveals potential mechanisms of liver pathology
Alexsia Richards,
Max Friesen,
Andrew Khalil,
M. Inmaculada Barrasa,
Lee Gehrke,
Rudolf Jaenisch
Affiliations
Alexsia Richards
Whitehead Institute for Biomedical Research, Cambridge, MA 02127, USA
Max Friesen
Whitehead Institute for Biomedical Research, Cambridge, MA 02127, USA
Andrew Khalil
Whitehead Institute for Biomedical Research, Cambridge, MA 02127, USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA; John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA
M. Inmaculada Barrasa
Whitehead Institute for Biomedical Research, Cambridge, MA 02127, USA
Lee Gehrke
Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA; Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02127, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02127, USA
Rudolf Jaenisch
Whitehead Institute for Biomedical Research, Cambridge, MA 02127, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02127, USA; Corresponding author
Summary: Although respiratory symptoms are the most prevalent disease manifestation of infection by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), infection can also damage other organs, including the brain, gut, and liver. Symptoms of liver damage are observed in nearly half of patients that succumb to severe SARS-CoV-2 infection. Here we use human-induced pluripotent stem cell-derived liver organoids (HLOs) to recapitulate and characterize liver pathology following virus exposure. Utilizing single-cell sequencing technology, we identified robust transcriptomic changes that occur in SARS-CoV-2 infected liver cells as well as uninfected bystander cells. Our results show a significant induction of many inflammatory pathways, including IFN-α, INF-γ, and IL-6 signaling. Our results further identify IL-6 signaling as a potential mechanism for liver-mediated activation of circulating macrophages.
