中枢神经系统（CNS）炎症中条形码病毒示踪揭示单细胞相互作用，这一成果由哈佛医学院Francisco J. Quintana研究团队经过不懈努力而取得。该研究成果发表在2021年4月23日出版的国际学术期刊《科学》上。
为了研究体内星形胶质细胞间的相互作用，研究人员研发了狂犬病条形码相互作用检测与测序（RABID-seq）相结合的技术，该技术结合了条形码化病毒示踪和单细胞RNA测序（scRNA-seq）的优势。使用RABID-seq，研究确定了轴突引导分子是小胶质细胞与星形胶质细胞相互作用的候选介质，可促进实验性自身免疫性脑脊髓炎（EAE）和潜在多发性硬化症（MS）中枢神经系统疾病的发生。
体内细胞特异性遗传扰动EAE研究、体外系统以及MS、scRNA-seq数据集和CNS组织分析确定，小胶质细胞中表达的Sema4D和Ephrin-B3分别通过PlexinB2和EphB3控制星形胶质细胞反应。
此外，中枢神经系统渗透性EphB3抑制剂抑制星形胶质细胞和小胶质细胞的促炎反应并可改善EAE。总之，RABID-seq可揭示小胶质细胞-星形胶质细胞的相互作用，并且其可作为候选治疗靶标。
附：英文原文
Title: Barcoded viral tracing of single-cell interactions in central nervous system inflammation
Author: Iain C. Clark, Cristina Gutiérrez-Vázquez, Michael A. Wheeler, Zhaorong Li, Veit Rothhammer, Mathias Linnerbauer, Liliana M. Sanmarco, Lydia Guo, Manon Blain, Stephanie E. J. Zandee, Chun-Cheih Chao, Katelyn V. Batterman, Marius Schwabenland, Peter Lotfy, Amalia Tejeda-Velarde, Patrick Hewson, Carolina Manganeli Polonio, Michael W. Shultis, Yasmin Salem, Emily C. Tjon, Pedro H. Fonseca-Castro, Davis M. Borucki, Kalil Alves de Lima, Agustin Plasencia, Adam R. Abate, Douglas L. Rosene, Kevin J. Hodgetts, Marco Prinz, Jack P. Antel, Alexandre Prat, Francisco J. Quintana
Issue&Volume: 2021/04/23
Abstract: Cell-cell interactions control the physiology and pathology of the central nervous system (CNS). To study astrocyte cell interactions in vivo, we developed rabies barcode interaction detection followed by sequencing (RABID-seq), which combines barcoded viral tracing and single-cell RNA sequencing (scRNA-seq). Using RABID-seq, we identified axon guidance molecules as candidate mediators of microglia-astrocyte interactions that promote CNS pathology in experimental autoimmune encephalomyelitis (EAE) and, potentially, multiple sclerosis (MS). In vivo cell-specific genetic perturbation EAE studies, in vitro systems, and the analysis of MS scRNA-seq datasets and CNS tissue established that Sema4D and Ephrin-B3 expressed in microglia control astrocyte responses via PlexinB2 and EphB3, respectively. Furthermore, a CNS-penetrant EphB3 inhibitor suppressed astrocyte and microglia proinflammatory responses and ameliorated EAE. In summary, RABID-seq identified microglia-astrocyte interactions and candidate therapeutic targets.
DOI: 10.1126/science.abf1230
Source: https://science.sciencemag.org/content/372/6540/eabf1230