Overexpressing NeuroD1 reprograms Müller cells into various types of retinal neurons

作     者：Di Xu Li-Ting Zhong Hai-Yang Cheng Zeng-Qiang Wang Xiong-Min Chen Ai-Ying Feng Wei-Yi Chen Gong Chen Ying Xu Di Xu;Li-Ting Zhong;Hai-Yang Cheng;Zeng-Qiang Wang;Xiong-Min Chen;Ai-Ying Feng;Wei-Yi Chen;Gong Chen;Ying Xu

作者机构：Guangdong-Hongkong-Macao Institute of CNS RegenerationKey Laboratory of CNS Regeneration(Ministry of Education)Jinan UniversityGuangzhouGuangdong ProvinceChina Co-Innovation Center of NeuroregenerationNantong UniversityNantongJiangsu ProvinceChina 

出 版 物：《Neural Regeneration Research》 (中国神经再生研究（英文版）)

年 卷 期：2023年第18卷第5期

页      面：1124-1131页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100212[医学-眼科学] 10[医学] 

基　　金：supported by the Guangdong Grant Key Technologies for Treatment of Brain Disorders,China,No. 2018B030332001 (to GC) the Guangzhou Key Projects of Brain Science and Brain-Like Intelligence Technology,No. 20200730009 (to YX) the Guangdong Basic and Applied Basic Research Foundation,No. 2020A1515110898 (to WYC)。 

主　　题：amacrine cell ganglion cell horizontal cell in vivo reprogramming Müller cell NeuroD1 photoreceptor regeneration retina retinal degeneration 

摘      要：The onset of retinal degenerative disease is often associated with neuronal loss. Therefore, how to regenerate new neurons to restore vision is an important issue. NeuroD1 is a neural transcription factor with the ability to reprogram brain astrocytes into neurons in vivo. Here, we demonstrate that in adult mice, NeuroD1 can reprogram Müller cells, the principal glial cell type in the retina, to become retinal neurons. Most strikingly, ectopic expression of NeuroD1 using two different viral vectors converted Müller cells into different cell types. Specifically, AAV7 m8 GFAP681::GFP-ND1 converted Müller cells into inner retinal neurons, including amacrine cells and ganglion cells. In contrast, AAV9 GFAP104::ND1-GFP converted Müller cells into outer retinal neurons such as photoreceptors and horizontal cells, with higher conversion efficiency. Furthermore, we demonstrate that Müller cell conversion induced by AAV9 GFAP104::ND1-GFP displayed clear dose-and time-dependence. These results indicate that Müller cells in adult mice are highly plastic and can be reprogrammed into various subtypes of retinal neurons.