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严重急性呼吸综合征冠状病毒2(SARS-CoV-2)感染人多能干细胞衍生的肝类器官揭示了肝脏病理的潜在机制。

SARS-CoV-2 infection of human pluripotent stem cell-derived liver organoids reveals potential mechanisms of liver pathology.

作者信息

Richards Alexsia, Friesen Max, Khalil Andrew, Barrasa M Inmaculada, Gehrke Lee, Jaenisch Rudolf

机构信息

Whitehead Institute for Biomedical Research, Cambridge, MA 02127, USA.

Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.

出版信息

iScience. 2022 Oct 21;25(10):105146. doi: 10.1016/j.isci.2022.105146. Epub 2022 Sep 16.

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5ae/9523400/1f11cef03e0a/fx1.jpg

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