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
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Department of Systems Immunology, Weizmann Institute of Science, Rehovot, Israel.
Nat Immunol. 2023 Apr;24(4):700-713. doi: 10.1038/s41590-023-01437-w. Epub 2023 Feb 20.
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.
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。为了理解这种相互作用，我们生成了成年小鼠视网膜在轴突横断之前及之后多个时间点的免疫细胞、神经胶质细胞和视网膜色素上皮细胞的单细胞图谱。我们在未受损的视网膜中鉴定出了罕见的细胞亚群，包括干扰素（IFN）反应性神经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。计算分析绘制了损伤后一个三相多细胞炎症级联反应。在早期阶段，视网膜大胶质细胞和小胶质细胞被重新激活，在从循环中募集CCR2单核细胞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，而一个可能由小胶质细胞衍生的I型干扰素驱动的IFN反应程序在驻留神经胶质细胞中被激活。后期表明炎症消退。我们的研究结果为解读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。
