中国科学家实现胶质细胞到神经元的体内转化
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中国科学家实现胶质细胞到神经元的体内转化

浏览次数:    时间:2020-04-13

本期文章:《细胞》:Online/在线发表

中国科学院脑智卓越中心杨辉、周海波等研究人员合作利用CRISPR-CasRx将胶质细胞转化为神经元,从而可减轻小鼠神经系统疾病的症状。这一研究成果于2020年4月8日在线发表在《细胞》上。

研究人员报使用一种新开发的靶向RNA的CRISPR系统CasRx用于体内病毒递送,来下调了一个RNA结合蛋白(Ptbp1),这使得Müller胶质细胞高效转化为视网膜神经节细胞(RGC),从而减轻了与RGC丢失有关的疾病症状。

此外,这种方法还可以诱导纹状体具有多巴胺能的神经元,并减轻帕金森氏病小鼠模型中的运动缺陷。因此,由CasRx介导的Ptbp1敲低引起的神经胶质到神经元的转化是一种有前途的体内遗传方法,可用于治疗由于神经元丢失而引起的各种疾病。

据介绍,胶质细胞转化为功能性神经元是一种潜在的治疗方法,可用于补充与神经退行性疾病和脑损伤相关的神经元丢失。低转换效率和在体内无法产生所需神经元类型阻碍了早期研究中使用转录因子表达在该领域的尝试。

附:英文原文

Title: Glia-to-Neuron Conversion by CRISPR-CasRx Alleviates Symptoms of Neurological Disease in Mice

Author: Haibo Zhou, Jinlin Su, Xinde Hu, Changyang Zhou, He Li, Zhaorong Chen, Qingquan Xiao, Bo Wang, Wenyan Wu, Yidi Sun, Yingsi Zhou, Cheng Tang, Fei Liu, Linhan Wang, Canbin Feng, Mingzhe Liu, Sanlan Li, Yifeng Zhang, Huatai Xu, Haishan Yao, Linyu Shi, Hui Yang

Issue&Volume: 2020-04-08

Abstract: Conversion of glial cells into functional neurons represents a potential therapeuticapproach for replenishing neuronal loss associated with neurodegenerative diseasesand brain injury. Previous attempts in this area using expression of transcriptionfactors were hindered by the low conversion efficiency and failure of generating desiredneuronal types in vivo. Here, we report that downregulation of a single RNA-binding protein, polypyrimidinetract-binding protein 1 (Ptbp1), using in vivo viral delivery of a recently developed RNA-targeting CRISPR system CasRx, resultedin the conversion of Müller glia into retinal ganglion cells (RGCs) with a high efficiency,leading to the alleviation of disease symptoms associated with RGC loss. Furthermore,this approach also induced neurons with dopaminergic features in the striatum andalleviated motor defects in a Parkinson’s disease mouse model. Thus, glia-to-neuronconversion by CasRx-mediated Ptbp1 knockdown represents a promising in vivo genetic approach for treating a variety of disorders due to neuronal loss.

DOI: 10.1016/j.cell.2020.03.024

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)30286-5

期刊信息

Cell:《细胞》,创刊于1974年。隶属于细胞出版社,最新IF:36.216

官方网址:https://www.cell.com/

投稿链接:https://www.editorialmanager.com/cell/default.aspx

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