Xu Hui, Cao Lining, Chen Yuxi, Zhou Cuiping, Xu Jie, Zhang Zhuolin, Li Xiangyu, Liu Lihua, Lu Jianfeng
Shanghai YangZhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
Key Lab of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, Nantong, Jiangsu Province, China.
Neural Regen Res. 2025 Dec 1;20(12):3635-3648. doi: 10.4103/NRR.NRR-D-23-02083. Epub 2024 Jun 26.
JOURNAL/nrgr/04.03/01300535-202512000-00031/figure1/v/2025-01-31T122243Z/r/image-tiff Inflammation plays a crucial role in the regeneration of fish and avian retinas. However, how inflammation regulates Müller glia (MG) reprogramming remains unclear. Here, we used single-cell RNA sequencing to investigate the cell heterogeneity and interactions of MG and immune cells in the regenerating zebrafish retina. We first showed that two types of quiescent MG (resting MG1 and MG2) reside in the uninjured retina. Following retinal injury, resting MG1 transitioned into an activated state expressing known reprogramming genes, while resting MG2 gave rise to rod progenitors. We further showed that retinal microglia can be categorized into three subtypes (microglia-1, microglia-2, and proliferative) and pseudotime analysis demonstrated dynamic changes in microglial status following retinal injury. Analysis of cell-cell interactions indicated extensive crosstalk between immune cells and MG, with many interactions shared among different immune cell types. Finally, we showed that inflammation activated Jak1-Stat3 signaling in MG, promoting their transition from a resting to an activated state. Our study reveals the cell heterogeneity and crosstalk of immune cells and MG in zebrafish retinal repair, and may provide valuable insights into future mammalian retina regeneration.
《期刊》/nrgr/04.03/01300535 - 202512000 - 00031/图1/v/2025 - 01 - 31T122243Z/图像 - tiff 炎症在鱼类和鸟类视网膜再生中起着关键作用。然而，炎症如何调节穆勒胶质细胞（MG）重编程仍不清楚。在这里，我们使用单细胞RNA测序来研究再生斑马鱼视网膜中MG和免疫细胞的细胞异质性及相互作用。我们首先表明，两种静止的MG（静止的MG1和MG2）存在于未受伤的视网膜中。视网膜损伤后，静止的MG1转变为表达已知重编程基因的激活状态，而静止的MG2产生视杆前体细胞。我们进一步表明，视网膜小胶质细胞可分为三种亚型（小胶质细胞 - 1、小胶质细胞 - 2和增殖型），伪时间分析表明视网膜损伤后小胶质细胞状态的动态变化。细胞 - 细胞相互作用分析表明免疫细胞和MG之间存在广泛的串扰，不同免疫细胞类型之间有许多共同的相互作用。最后，我们表明炎症激活了MG中的Jak1 - Stat3信号通路，促进它们从静止状态转变为激活状态。我们的研究揭示了斑马鱼视网膜修复中免疫细胞和MG的细胞异质性及串扰，并可能为未来哺乳动物视网膜再生提供有价值的见解。
