重编程
生物
星形胶质细胞
生物神经网络
转录因子
神经科学
表观遗传学
细胞生物学
细胞
中枢神经系统
遗传学
基因
作者
Lei Zhang,Jiu Chao Yin,Hana Yeh,Xin Ning,Grace Lee,Xiangyun Amy Chen,Yanming Wang,Li Lin,Li Chen,Peng Jin,Gang Wu,Gong Chen
出处
期刊:Cell Stem Cell
[Elsevier]
日期:2015-12-01
卷期号:17 (6): 735-747
被引量:239
标识
DOI:10.1016/j.stem.2015.09.012
摘要
We have recently demonstrated that reactive glial cells can be directly reprogrammed into functional neurons by a single neural transcription factor, NeuroD1. Here we report that a combination of small molecules can also reprogram human astrocytes in culture into fully functional neurons. We demonstrate that sequential exposure of human astrocytes to a cocktail of nine small molecules that inhibit glial but activate neuronal signaling pathways can successfully reprogram astrocytes into neurons in 8-10 days. This chemical reprogramming is mediated through epigenetic regulation and involves transcriptional activation of NEUROD1 and NEUROGENIN2. The human astrocyte-converted neurons can survive for >5 months in culture and form functional synaptic networks with synchronous burst activities. The chemically reprogrammed human neurons can also survive for >1 month in the mouse brain in vivo and integrate into local circuits. Our study opens a new avenue using chemical compounds to reprogram reactive glial cells into functional neurons.
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