SARS-CoV-2 infection of human pluripotent stem cell-derived liver organoids reveals potential mechanisms of liver pathology
Name
1-s2.0-S2589004222014183-main.pdf
Description
Published version
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2.42 MB
Format
Adobe PDF
Checksum (MD5)
39a5c8bfb31f4599ee40d07e25350be3
Author(s)
Richards, Alexsia
Friesen, Max
Khalil, Andrew
Barrasa, M Inmaculada
Gehrke, Lee
Jaenisch, Rudolf
Date Issued
October 2022
Journal
iScience
Publisher
Elsevier BV
Citation
Richards, Alexsia, Friesen, Max, Khalil, Andrew, Barrasa, M Inmaculada, Gehrke, Lee et al. 2022. "SARS-CoV-2 infection of human pluripotent stem cell-derived liver organoids reveals potential mechanisms of liver pathology." iScience, 25 (10).
Version
Final published version
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.1016/j.isci.2022.105146
