tetano
Editor, Senior Moderator
iScience
. 2022 Sep 16;105146.
doi: 10.1016/j.isci.2022.105146. Online ahead of print.
SARS-CoV-2 infection of human pluripotent stem cell-derived liver organoids reveals potential mechanisms of liver pathology
Alexsia Richards[SUP] 1 [/SUP], Max Friesen[SUP] 1 [/SUP], Andrew Khalil[SUP] 1 2 3 [/SUP], M Inmaculada Barrasa[SUP] 1 [/SUP], Lee Gehrke[SUP] 4 5 6 [/SUP], Rudolf Jaenisch[SUP] 1 6 [/SUP]
Affiliations
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.
. 2022 Sep 16;105146.
doi: 10.1016/j.isci.2022.105146. Online ahead of print.
SARS-CoV-2 infection of human pluripotent stem cell-derived liver organoids reveals potential mechanisms of liver pathology
Alexsia Richards[SUP] 1 [/SUP], Max Friesen[SUP] 1 [/SUP], Andrew Khalil[SUP] 1 2 3 [/SUP], M Inmaculada Barrasa[SUP] 1 [/SUP], Lee Gehrke[SUP] 4 5 6 [/SUP], Rudolf Jaenisch[SUP] 1 6 [/SUP]
Affiliations
- PMID: 36128218
- PMCID: PMC9477603
- DOI: 10.1016/j.isci.2022.105146
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.