《生命科学》 2023, 35(4): 419-428

提高神经细胞直接重编程效率的研究进展

杜淑娴¹ , 莫李存¹ , 程乐平^1,2,3,*

¹广西医科大学再生医学与医用生物资源开发应用省部共建协同创新中心，广西再生医学重点实验室，南宁 530021 ²广西医科大学基础医学院，神经科学研究所，广西脑科学研究重点实验室，广西壮族自治区卫生健康委员会脑功能与 脑疾病基础研究重点实验室(广西医科大学)，南宁 530021 ³长寿与老年相关疾病教育部重点实验室，南宁 530021

摘　要：

近年来，神经细胞直接重编程技术已经成为潜在的细胞替代治疗新手段。体内直接重编程利用与缺失细胞相邻的内源细胞再生目标细胞进行替换，可避免由外部细胞移植引起的免疫排斥反应，有效降低致癌风险，具有良好的应用前景。但同时，神经细胞直接重编程也面临着诸多挑战，如重编程后的神经元存活困难、需要损伤或疾病期间丢失的特定神经元亚型的再生、重编程效率低下等。如何实现高效的在体神经细胞直接重编程，是目前需要克服的难题。该综述主要对如何提高神经细胞直接重编程的效率进行概述，主要包括抗氧化剂、铁死亡抑制剂和抗凋亡蛋白的应用、激活神经元富含的线粒体基因、运用表观遗传因子和转录因子组合等，这些将为更好地发挥神经细胞直接重编程的效用提供参考。

通讯作者：程乐平 , Email:lpcheng@gxmu.edu.cn

Research progress on improving efficiency of direct neuronal reprogramming

DU Shu-Xian¹ , MO Li-Cun¹ , CHENG Le-Ping^1,2,3,*

¹Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed by the Province and Ministry, Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Nanning 530021, China ²Institute of Neuroscience and Guangxi Key Laboratory of Brain Science, Guangxi Health Commission Key Laboratory of Basic Research on Brain Function and Disease, School of Basic Medical Sciences, Guangxi Medical University, Nanning 530021, China ³Key Laboratory of Longevity and Aging-related Diseases of Chinese Ministry of Education, Nanning 530021, China

Abstract:

In recent years, direct neuronal reprogramming technology has become a potential new choice for cell replacement therapy. Direct reprogramming in vivo converts endogenous cells into desired target cells, avoiding the immune rejections caused by exogenous cell transplantation and effectively reducing the risk of developing cancers. At the meanwhile, however, direct neuronal reprogramming in vivo is faced with much challenge such as low neuronal survival rate, low reprogramming efficiency, and the necessity to regenerate specific neuronal subtypes lost during injury or diseases. This review mainly summarizes the progress on improving the efficiency of direct neuronal reprogramming by means of the applications of the antioxidants, ferroptosis inhibitors, anti-apoptotic proteins, the activation of neuron-enriched mitochondrial genes, and the use of epigenetic factors and combination of transcription factors, which will be of immense help for its future usage.

Communication Author：CHENG Le-Ping , Email:lpcheng@gxmu.edu.cn