Richards Alexsia, Friesen Max, Khalil Andrew, Barrasa M Inmaculada, Gehrke Lee, Jaenisch Rudolf
Whitehead Institute for Biomedical Research, Cambridge, MA 02127, USA.
Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.
iScience. 2022 Oct 21;25(10):105146. doi: 10.1016/j.isci.2022.105146. Epub 2022 Sep 16.
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.
尽管呼吸道症状是严重急性呼吸综合征冠状病毒2(SARS-CoV-2)感染最常见的疾病表现,但感染也会损害包括脑、肠道和肝脏在内的其他器官。在死于严重SARS-CoV-2感染的患者中,近一半观察到肝脏损伤症状。在此,我们使用人诱导多能干细胞衍生的肝类器官(HLOs)来重现和表征病毒暴露后的肝脏病理。利用单细胞测序技术,我们确定了SARS-CoV-2感染的肝细胞以及未感染的旁观者细胞中发生的显著转录组变化。我们的结果显示许多炎症通路有显著诱导,包括IFN-α、INF-γ和IL-6信号传导。我们的结果进一步确定IL-6信号传导是肝脏介导的循环巨噬细胞激活的潜在机制。