一种用于SARS-CoV-2感染的人类3D神经类器官模型。
A Human 3D neural assembloid model for SARS-CoV-2 infection.
作者信息
Wang Lu, Sievert David, Gleeson Joseph, Clark Alex E, Carlin Aaron F, Federman Hannah, Gastfriend Benjamin D, Shusta Eric, Palecek Sean P
机构信息
Department of Neurosciences, University of California San Diego, La Jolla, CA, 92093, USA; Rady Children's Institute for Genomic Medicine, Rady Children's Hospital, San Diego, CA, 92123, USA.
Department of Neurosciences, University of California San Diego, La Jolla, CA, 92093, USA; Rady Children's Institute for Genomic Medicine, Rady Children's Hospital, San Diego, CA, 92123, USA; Department for Pediatrics, University of California San Diego, La Jolla, CA, 92093, USA.
出版信息
Res Sq. 2021 Feb 12:rs.3.rs-214352. doi: 10.21203/rs.3.rs-214352/v1.
Clinical evidence suggests the central nervous system (CNS) is frequently impacted by SARS-CoV-2 infection, either directly or indirectly, although mechanisms remain unclear. Pericytes are perivascular cells within the brain that are proposed as SARS-CoV-2 infection points . Here we show that pericyte-like cells (PLCs), when integrated into a cortical organoid, are capable of infection with authentic SARS-CoV-2. Prior to infection, PLCs elicited astrocytic maturation and production of basement membrane components, features attributed to pericyte functions in vivo. While traditional cortical organoids showed little evidence of infection, PLCs within cortical organoids served as viral 'replication hubs', with virus spreading to astrocytes and mediating inflammatory type I interferon transcriptional responses. Therefore, PLC-containing cortical organoids (PCCOs) represent a new 'assembloid' model that supports SARS-CoV-2 entry and replication in neural tissue, and PCCOs serve as an experimental model for neural infection.
临床证据表明，严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染常直接或间接影响中枢神经系统（CNS），但其机制尚不清楚。周细胞是脑内的血管周围细胞，被认为是SARS-CoV-2的感染点。在此，我们表明，类周细胞（PLCs）整合到皮质类器官中时，能够被真正的SARS-CoV-2感染。在感染前，PLCs引发星形胶质细胞成熟和基底膜成分的产生，这些特征归因于体内周细胞的功能。虽然传统的皮质类器官几乎没有感染迹象，但皮质类器官内的PLCs充当病毒“复制中心”，病毒扩散到星形胶质细胞并介导炎症性I型干扰素转录反应。因此，含PLC的皮质类器官（PCCOs）代表了一种新的“组装体”模型，该模型支持SARS-CoV-2在神经组织中的进入和复制，并且PCCOs可作为神经感染的实验模型。
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