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人类多能干细胞来源的类神经器官体模型可用于测试SARS-CoV-2感染
作者:小柯机器人 发布时间:2020/9/24 12:44:20

美国宾夕法尼亚大学Guo-li Ming等研究人员合作开发出人类多能干细胞来源的类神经器官体模型,可用于测试SARS-CoV-2感染。这一研究成果于2020年9月21日在线发表在国际学术期刊《细胞—干细胞》上。

研究人员测试了人类诱导型多能干细胞(hiPSC)来源的单层脑细胞和区域特异性脑器官对SARS-CoV-2感染的敏感性。研究人员发现神经元和星形胶质细胞被稀疏感染,但脉络丛上皮细胞受到强烈感染。研究人员优化了从hiPSC产生脉络丛神经类器官的方法,并显示这些类器官的SARS-CoV-2感染与细胞死亡的增加和转录失调有关,从而表明了炎症反应和细胞功能缺陷。
 
因此,这些发现提供了SARS-CoV-2神经感染的证据,并表明使用hiPSC衍生的脑类器官可作为研究脑细胞SARS-CoV-2易感性、病毒引发脑功能障碍机制以及治疗。
 
据悉,神经系统并发症在COVID-19患者中很常见。尽管已在某些患者的大脑中检测到SARS-CoV-2(COVID-19的致病性病原体),但它对脑细胞的感染以及影响其功能的能力尚未得到很好的了解。
 
附:英文原文

Title: Human Pluripotent Stem Cell-Derived Neural Cells and Brain Organoids Reveal SARS-CoV-2 Neurotropism Predominates in Choroid Plexus Epithelium

Author: Fadi Jacob, Sarshan R. Pather, Wei-Kai Huang, Feng Zhang, Samuel Zheng Hao Wong, Haowen Zhou, Beatrice Cubitt, Wenqiang Fan, Catherine Z. Chen, Miao Xu, Manisha Pradhan, Daniel Y. Zhang, Wei Zheng, Anne G. Bang, Hongjun Song, Juan Carlos de la Torre, Guo-li Ming

Issue&Volume: 2020-09-21

Abstract: Neurological complications are common in patients with COVID-19. While SARS-CoV-2, the causal pathogen of COVID-19, has been detected in some patient brains, its ability to infect brain cells and impact their function are not well understood. Here we investigated the susceptibility of human induced pluripotent stem cell (hiPSC)-derived monolayer brain cells and region-specific brain organoids to SARS-CoV-2 infection. We found that neurons and astrocytes were sparsely infected, but choroid plexus epithelial cells underwent robust infection. We optimized a protocol to generate choroid plexus organoids from hiPSCs and showed that productive SARS-CoV-2 infection of these organoids is associated with increased cell death and transcriptional dysregulation indicative of an inflammatory response and cellular function deficits. Together, our findings provide evidence for selective SARS-CoV-2 neurotropism and support the use of hiPSC-derived brain organoids as a platform to investigate SARS-CoV-2 infection susceptibility of brain cells, mechanisms of virus-induced brain dysfunction, and treatment strategies.

DOI: 10.1016/j.stem.2020.09.016

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30463-X

期刊信息

Cell Stem Cell:《细胞—干细胞》,创刊于2007年。隶属于细胞出版社,最新IF:21.464
官方网址:https://www.cell.com/cell-stem-cell/home
投稿链接:https://www.editorialmanager.com/cell-stem-cell/default.aspx