In vivo simultaneous transcriptional activation of multiple genes in the brain using CRISPR–dCas9-activator transgenic mice
Abstract
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.
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Autophagy is known to regulate lipid droplet concentrations.
“a mechanism which is known to regulate LD concentrations27–29”
From APOE4/4 is linked to damaging lipid droplets in Alzheimer’s disease microglia (2024) · cites this paper as [29]
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- Authors
- Zhou, H., Liu, J., Zhou, C., Gao, N., Rao, Z., Li, H., Hu, X., Li, C., Yao, X., Shen, X., Sun, Y., Wei, Y., Liu, F., Ying, W., Zhang, J., Tang, C., Zhang, X., Xu, H., Shi, L., Cheng, L., Huang, P., & Yang, H.
- Affiliations
- Chinese Academy of Sciences (CN)
- ShanghaiTech University (CN)
- Corresponding author
- Huang, Pengyu
- Yang, Hui
- ORCID
- Venue
- Nature Neuroscience
- Published
- 2018-01-15
- Volume
- 21
- Issue
- 3
- Pages
- 440-446
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- OpenAlex
- W2783322400
- Cited by
- 276
- References
- 57
- Citations by year
- 2026: 10 · 2025: 26 · 2024: 37 · 2023: 36 · 2022: 38 · 2021: 35 · 2020: 39 · 2019: 34 · 2018: 20
- FWCI
- 11.38
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Animal Genetics and Reproduction
- Keywords
- CRISPR/dCas9, transcriptional activation, transgenic mice, long non-coding RNA, astrocyte-to-neuron conversion, neurogenesis, gene networks, brain
- MeSH terms
- Animals, Astrocytes, Brain Chemistry, DNA-Binding Proteins, Female, Male, Mice, Transgenic, Nerve Tissue Proteins, Nervous System, Neurons, Nuclear Proteins, Transcriptional Activation, Mice, Primary Cell Culture, RNA, Long Noncoding, CRISPR-Cas Systems
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