美国麻省理工学院和哈佛大学布罗德研究所Aviv Regev和Inbal Benhar共同合作，近期取得重要工作进展。他们通过研究非神经元视网膜细胞的时间单细胞图谱，揭示了中枢神经系统损伤的动态、协调的多细胞反应。相关研究成果2023年2月20日在线发表于《自然—免疫学》杂志上。

据介绍，非神经元细胞是中枢神经系统损伤后复杂细胞相互作用的关键。

为了了解这种相互作用，研究人员在轴突横断之前和之后的多个时间点从成年小鼠视网膜中生成了免疫、胶质和视网膜色素上皮细胞的单细胞图谱。他们鉴定了幼稚视网膜中罕见的亚群，包括干扰素（IFN）反应胶质细胞和边界相关巨噬细胞，并描绘了损伤诱导的细胞组成、表达程序和相互作用的变化。计算分析描绘了损伤后的三阶段多细胞炎症级联。在早期阶段，视网膜大胶质细胞和小胶质细胞被重新激活，在循环中CCR2⁺单核细胞浸润的同时提供趋化信号。这些细胞在中间阶段分化为巨噬细胞，而可能由小胶质细胞来源的I型IFN驱动的IFN应答程序在驻留胶质细胞中被激活。晚期表明炎症消退。

总之，这一发现为解释组织损伤后的细胞回路、空间关系和分子相互作用提供了一个框架。

附：英文原文

Title: Temporal single-cell atlas of non-neuronal retinal cells reveals dynamic, coordinated multicellular responses to central nervous system injury

Author: Benhar, Inbal, Ding, Jiarui, Yan, Wenjun, Whitney, Irene E., Jacobi, Anne, Sud, Malika, Burgin, Grace, Shekhar, Karthik, Tran, Nicholas M., Wang, Chen, He, Zhigang, Sanes, Joshua R., Regev, Aviv

Issue&Volume: 2023-02-20

Abstract: Non-neuronal cells are key to the complex cellular interplay that follows central nervous system insult. To understand this interplay, we generated a single-cell atlas of immune, glial and retinal pigment epithelial cells from adult mouse retina before and at multiple time points after axonal transection. We identified rare subsets in naive retina, including interferon (IFN)-response glia and border-associated macrophages, and delineated injury-induced changes in cell composition, expression programs and interactions. Computational analysis charted a three-phase multicellular inflammatory cascade after injury. In the early phase, retinal macroglia and microglia were reactivated, providing chemotactic signals concurrent with infiltration of CCR2+ monocytes from the circulation. These cells differentiated into macrophages in the intermediate phase, while an IFN-response program, likely driven by microglia-derived type I IFN, was activated across resident glia. The late phase indicated inflammatory resolution. Our findings provide a framework to decipher cellular circuitry, spatial relationships and molecular interactions following tissue injury.

DOI: 10.1038/s41590-023-01437-w

Source: https://www.nature.com/articles/s41590-023-01437-w