In vivo simultaneous transcriptional activation of multiple genes in the brain using CRISPR-dCas9-activator transgenic mice

被引：210

作者：

Zhou, Haibo ^{[1
]}

Liu, Junlai ^{[2
,3
,4
]}

Zhou, Changyang ^{[1
,3
]}

Gao, Ni ^{[1
,3
]}

Rao, Zhiping ^{[1
,3
]}

Li, He ^{[1
,3
]}

Hu, Xinde ^{[1
,3
]}

Li, Changlin ^{[1
]}

Yao, Xuan ^{[1
]}

Shen, Xiaowen ^{[1
]}

Sun, Yidi ^{[5
]}

Wei, Yu ^{[1
]}

Liu, Fei ^{[1
,3
]}

Ying, Wenqin ^{[1
]}

Zhang, Junming ^{[1
]}

Tang, Cheng ^{[1
,3
]}

Zhang, Xu ^{[1
]}

Xu, Huatai ^{[1
]}

Shi, Linyu ^{[1
]}

Cheng, Leping ^{[1
]}

Huang, Pengyu ^{[2
]}

Yang, Hui ^{[1
]}

机构：

[1] Chinese Acad Sci, CAS Ctr Excellence Brain Sci & Intelligence Techn, Shanghai Inst Biol Sci, Inst Neurosci,State Key Lab Neurosci, Shanghai, Peoples R China

[2] ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China

[3] Univ Chinese Acad Sci, Coll Life Sci, Beijing, Peoples R China

[4] Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, Shanghai, Peoples R China

[5] Chinese Acad Sci, Shanghai Inst Biol Sci, CAS MPG Partner Inst Computat Biol, Key Lab Computat Biol, Shanghai, Peoples R China

来源：

NATURE NEUROSCIENCE | 2018年 / 21卷 / 03期

关键词：

CONVERTS FIBROBLASTS; NEURONAL CELLS; CRISPR; GENOME; EXPRESSION; SYSTEM; COMPLEX; DIFFERENTIATION; OVEREXPRESSION; MODULATION;

D O I：

10.1038/s41593-017-0060-6

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Despite rapid progresses in the genome-editing field, in vivo simultaneous overexpression of multiple genes remains challenging. We generated a transgenic mouse using an improved dCas9 system that enables simultaneous and precise in vivo transcriptional activation of multiple genes and long noncoding RNAs in the nervous system. As proof of concept, we were able to use targeted activation of endogenous neurogenic genes in these transgenic mice to directly and efficiently convert astrocytes into functional neurons in vivo. This system provides a flexible and rapid screening platform for studying complex gene networks and gain-of-function phenotypes in the mammalian brain.

引用

页码：440 / +

页数：13

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