Single-cell RNA sequencing reveals the heterogeneity and interactions of immune cells and Müller glia during zebrafish retina regeneration  

作　　者：Hui Xu Lining Cao Yuxi Chen Cuiping Zhou Jie Xu Zhuolin Zhang Xiangyu Li Lihua Liu Jianfeng Lu 

机构地区：[1]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 [2]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

出　　处：《Neural Regeneration Research》2025年第12期3635-3648,共14页中国神经再生研究(英文版)

基　　金：supported by the National Natural Science Foundation of China,Nos.81970820(to HX),31771644(to JL),31930068(to JL),82371176(to JL),81801331(to LC);National Key Research and Development Project of China.Nos.2017YFA0104100(to JL),2017YFA0701304(to HX);Shanghai Yangzhi Rehabilitation Hospital(Shanghai Sunshine Rehabilitation Center)Talent Introduction Plan,No.KYPT202204(to LC);the Fundamental Research Funds for the Central Universities,No.22120230292(to JL)。

摘　　要：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.

关 键 词：immune cells inflammation Jak1-Stat3 signaling microglia Müller glia REGENERATION reprogramming RETINA single-cell RNAseq ZEBRAFISH 

分 类 号：R774[医药卫生—眼科]