中国神经再生研究(英文版) ›› 2026, Vol. 21 ›› Issue (8): 3650-3658.doi: 10.4103/NRR.NRR-D-24-00883

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

NeuroD1 和 Ascl1 在人脑组织体外培养中将人神经胶质细胞转化为神经元

  

  • 出版日期:2026-08-18 发布日期:2026-04-27

Conversion of human glial cells into neurons in ex vivo culture of human brain tissue: Essential roles of the transcription factors NeuroD1 and Ascl1

Liang Xu1, #, Qingsong Wang1, *, #, Jiancheng Liao2, #, Jiajun Zheng3, Bing Qin2, Wen Li1, Jiaxuan Zhang1, Wei Li4, Xiangyu Wang2, *, Maoying Zhang2, *, Gong Chen1, *   

  1. 1Guangdong-Hongkong-Macau CNS Regeneration Institute of Jinan University, Key Laboratory of CNS Regeneration (Jinan University)-Ministry of Education, Guangdong Key Laboratory of Non-human Primate Research, Guangzhou, Guangdong Province, China; 
    2Department of Neurosurgery, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong Province, China; 
    3Department of Anesthesiology, Guangzhou First People’s Hospital, Guangzhou, Guangdong Province, China; 
    4Department of Neurosurgery, The Sixth Affiliated Hospital of Jinan University, Dongguan, Guangdong Province, China
  • Online:2026-08-18 Published:2026-04-27
  • Contact: Gong Chen, PhD, gongchen@jnu.edu.cn; Qingsong Wang, PhD, wqshty@163.com; Xiangyu Wang, MD, PhD, wang_xy123@126.com; Maoying Zhang, MD, PhD,zmaoying2009@163.com.
  • Supported by:
    This study was supported by the Key Project of Guangzhou City, No. 202206060002 (to GC); the Guangdong Province Science and Technology Project of China, No. 2018B030332001 (to GC); the Natural Science Foundation of Guangdong Province of China, No. 2020A1515010854 (to QW); and the Yi-Liang Liu Endowment Fund from Jinan University Education Development Foundation.

摘要: 在啮齿动物和非人灵长类动物(NHPs)的中枢神经系统(CNS)中,转录因子介导的细胞转换已有报道。特别是,神经胶质细胞到神经元(GtN)的转化已在动物模型的大脑和脊髓中实现,用于神经再生和修复。然而,GtN 转换能否最终用于患者的人脑修复还需要探索。为了研究 GtN 转换技术在人脑中的适用性,实验利用从癫痫患者身上切除的人脑组织建立了一个长期的体外培养系统,直接测试 GtN 转换。结果显示,神经转录因子 NeuroD1 和 Ascl1 可将人神经胶质细胞转化为神经元。重要的是,免疫染色和电生理记录都显示,胶质细胞转化的神经元在转化的最初7-14天表现出不成熟的特性,在转化21-27天后获得更成熟的神经元特性。这些人脑组织的体内外转化研究为未来使用基于转录因子的GtN转化方法治疗神经系统疾病的临床试验铺平了道路。


https://orcid.org/0000-0002-1857-3670 (Gong Chen); https://orcid.org/0000-0003-2622-171X (Qingsong Wang)

关键词: Ascl1, 脑片, 细胞转化, 体外培养, 神经胶质细胞, 神经胶质细胞向神经元的转化, 人脑, 体内重编程, 神经再生, NeuroD1

Abstract: Transcription factor–mediated cell conversion has been reported in the central nervous system of both rodents and nonhuman primates. In particular, glia-to-neuron conversion has been achieved in the brain and spinal cord of animal models for neural regeneration and repair. However, whether glia-to-neuron conversion can be used for brain repair in humans needs to be explored. To investigate the use of glia-to-neuron conversion technology in the human brain, we established a long-term ex vivo culture system using human brain tissue that was surgically removed from epileptic patients to test glia-to-neuron conversion directly. We found that neural transcription factors NeuroD1 and Ascl1 both converted human glial cells into neurons. Immunostaining and electrophysiological recordings showed that the glia-converted neurons demonstrated immature properties during the initial 7–14 days of conversion, and then acquired more mature neuronal properties after 21–27 days of conversion. These ex vivo conversion studies in human brain tissue pave the way toward future clinical trials using a transcription factor–based glia-to-neuron conversion approach to treat neurological disorders.

Key words: Ascl1, brain slice, cell conversion, ex vivo culture, glial cell, glia-to-neuron conversion, human brain, in vivo reprogramming, neural regeneration, NeuroD1