In vivo simultaneous transcriptional activation of multiple genes in the brain using CRISPR-dCas9-activator transgenic mice.
Haibo ZhouJunlai LiuChangyang ZhouNi GaoZhiping RaoHe LiXinde HuChanglin LiXuan YaoXiaowen ShenYidi SunYu WeiFei LiuWenqin YingJunming ZhangCheng TangXu ZhangHuatai XuLinyu ShiLeping ChengPengyu HuangHui YangPublished in: Nature neuroscience (2018)
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.
Keyphrases
- genome wide
- genome editing
- crispr cas
- genome wide identification
- transcription factor
- bioinformatics analysis
- dna methylation
- genome wide analysis
- gene expression
- resting state
- cell proliferation
- spinal cord
- copy number
- drug delivery
- functional connectivity
- cancer therapy
- nuclear factor
- brain injury
- heat shock protein