The DOI matches its Crossref record; 57 of the 57 references it cites were found in a registry or an index.
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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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]
Citations
Cites
Takahashi, K., & Yamanaka, S. (2006) · Cell · doi:10.1016/j.cell.2006.07.024 · Cited by 26,673
Repurposing CRISPR as an RNA-Guided Platform for Sequence-Specific Control of Gene Expression
Qi, L. S., Larson, M. H., Gilbert, L. A., Doudna, J. A., Weissman, J. S., Arkin, A. P., & Lim, W. A. (2013) · Cell · doi:10.1016/j.cell.2013.02.022 · Cited by 5,016
Preparation of separate astroglial and oligodendroglial cell cultures from rat cerebral tissue.
McCarthy, K. D., & de Vellis, J. (1980) · The Journal of Cell Biology · doi:10.1083/jcb.85.3.890 · Cited by 3,825
CRISPR-Mediated Modular RNA-Guided Regulation of Transcription in Eukaryotes
Gilbert, L. A., Larson, M. H., Morsut, L., Liu, Z., Brar, G. A., Torres, S. E., Stern-Ginossar, N., Brandman, O., Whitehead, E. H., Doudna, J. A., et al. (2013) · Cell · doi:10.1016/j.cell.2013.06.044 · Cited by 3,696
Expression of a single transfected cDNA converts fibroblasts to myoblasts
Davis, R. L., Weintraub, H. M., & Lassar, A. B. (1987) · Cell · doi:10.1016/0092-8674(87)90585-x · Cited by 3,388
Genome-scale transcriptional activation by an engineered CRISPR-Cas9 complex
Konermann, S., Brigham, M. D., Trevino, A. E., Joung, J., Abudayyeh, O. O., Barcena, C., Hsu, P. D., Habib, N., Gootenberg, J. S., Nishimasu, H., et al. (2015) · Nature · doi:10.1038/nature14136 · Cited by 2,825
Genome-Scale CRISPR-Mediated Control of Gene Repression and Activation
Gilbert, L. A., Horlbeck, M. A., Adamson, B., Villalta, J. E., Chen, Y., Whitehead, E. H., Guimaraes, C., Panning, B., Ploegh, H. L., Bassik, M. C., et al. (2014) · Cell · doi:10.1016/j.cell.2014.09.029 · Cited by 2,728
Hilton, I. B., D’Ippolito, A. M., Vockley, C. M., Thakore, P. I., Crawford, G. E., Reddy, T. E., & Gersbach, C. A. (2015) · Nature Biotechnology · doi:10.1038/nbt.3199 · Cited by 1,931
Mali, P., Aach, J., Stranges, P. B., Esvelt, K. M., Moosburner, M., Kosuri, S., Yang, L., & Church, G. M. (2013) · Nature Biotechnology · doi:10.1038/nbt.2675 · Cited by 1,752
Hydrodynamics-based transfection in animals by systemic administration of plasmid DNA
Liu, F., Song, Y. K., & Liu, D. (1999) · Gene Therapy · doi:10.1038/sj.gt.3300947 · Cited by 1,728
Self-citationHighly efficient Cas9-mediated transcriptional programming
Chavez, A., Scheiman, J., Vora, S., Pruitt, B. W., Tuttle, M., P R Iyer, E., Lin, S., Kiani, S., Guzman, C. D., Wiegand, D. J., et al. (2015) · Nature Methods · doi:10.1038/nmeth.3312 · Cited by 1,622
A Protein-Tagging System for Signal Amplification in Gene Expression and Fluorescence Imaging
Tanenbaum, M. E., Gilbert, L. A., Qi, L. S., Weissman, J. S., & Vale, R. D. (2014) · Cell · doi:10.1016/j.cell.2014.09.039 · Cited by 1,611
RNA-guided gene activation by CRISPR-Cas9-based transcription factors
Perez-Pinera, P., Kocak, D. D., Vockley, C. M., Adler, A. F., Kabadi, A. M., Polstein, L. R., Thakore, P. I., Glass, K. A., Ousterout, D. G., Leong, K. W., et al. (2013) · Nature Methods · doi:10.1038/nmeth.2600 · Cited by 1,328
CRISPR RNA–guided activation of endogenous human genes
Maeder, M. L., Linder, S. J., Cascio, V. M., Fu, Y., Ho, Q. H., & Joung, J. K. (2013) · Nature Methods · doi:10.1038/nmeth.2598 · Cited by 1,249
Editing DNA Methylation in the Mammalian Genome
Liu, X. S., Wu, H., Ji, X., Stelzer, Y., Wu, X., Czauderna, S., Shu, J., Dadon, D., Young, R. A., & Jaenisch, R. (2016) · Cell · doi:10.1016/j.cell.2016.08.056 · Cited by 1,224
Bikard, D., Jiang, W., Samai, P., Hochschild, A., Zhang, F., & Marraffini, L. A. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt520 · Cited by 1,145
Cre-dependent selection yields AAV variants for widespread gene transfer to the adult brain
Deverman, B. E., Pravdo, P. L., Simpson, B. P., Kumar, S. R., Chan, K. Y., Banerjee, A., Wu, W.-L., Yang, B., Huber, N., Pasca, S. P., et al. (2016) · Nature Biotechnology · doi:10.1038/nbt.3440 · Cited by 1,061
Effect of genome size on AAV vector packaging
Wu, Z., Yang, H., & Colosi, P. (2010) · Molecular Therapy · doi:10.1038/mt.2009.255 · Cited by 1,029
Self-citationEfficient transposition of the piggyBac (PB) transposon in mammalian cells and mice
Ding, S., Wu, X., Li, G., Han, M., Zhuang, Y., & Xu, T. (2005) · Cell · doi:10.1016/j.cell.2005.07.013 · Cited by 1,009
Engineering complex synthetic transcriptional programs with CRISPR RNA scaffolds
Zalatan, J. G., Lee, M. E., Almeida, R., Gilbert, L. A., Whitehead, E. H., La Russa, M., Tsai, J. C., Weissman, J. S., Dueber, J. E., Qi, L. S., et al. (2015) · Cell · doi:10.1016/j.cell.2014.11.052 · Cited by 938
Horlbeck, M. A., Gilbert, L. A., Villalta, J. E., Adamson, B., Pak, R. A., Chen, Y., Fields, A. P., Park, C. Y., Corn, J. E., Kampmann, M., et al. (2016) · eLife · doi:10.7554/elife.19760 · Cited by 894
Induction of functional hepatocyte-like cells from mouse fibroblasts by defined factors
Huang, P., He, Z., Ji, S., Sun, H., Xiang, D., Liu, C., Hu, Y., Wang, X., & Hui, L. (2011) · Nature · doi:10.1038/nature10116 · Cited by 864
Self-citationCheng, A. W., Wang, H., Yang, H., Shi, L., Yarden Katz, A., Theunissen, T. W., Rangarajan, S., Shivalila, C., Dadon, D. B., & Jaenisch, R. (2013) · Cell Research · doi:10.1038/cr.2013.122 · Cited by 768
Self-citationA split-Cas9 architecture for inducible genome editing and transcription modulation
Zetsche, B., Volz, S. E., & Zhang, F. (2015) · Nature Biotechnology · doi:10.1038/nbt.3149 · Cited by 722
Ting, J. T., Daigle, T. L., Chen, Q., & Feng, G. (2014) · Methods in molecular biology · doi:10.1007/978-1-4939-1096-0_14 · Cited by 631
A light-inducible CRISPR-Cas9 system for control of endogenous gene activation
Polstein, L. R., & Gersbach, C. A. (2015) · Nature Chemical Biology · doi:10.1038/nchembio.1753 · Cited by 630
Mild overexpression of MeCP2 causes a progressive neurological disorder in mice
Collins, A. L., Levenson, J. M., Vilaythong, A. P., Richman, R., Armstrong, D. L., Noebels, J. L., David Sweatt, J., & Zoghbi, H. Y. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddh282 · Cited by 626
Comparison of Cas9 activators in multiple species
Chavez, A., Tuttle, M. L., Pruitt, B. W., Ewen‐Campen, B., Chari, R., Ter‐Ovanesyan, D., Haque, S. J., Cecchi, R. J., Kowal, E. J. K., Buchthal, J., et al. (2016) · Nature Methods · doi:10.1038/nmeth.3871 · Cited by 521
Directing Astroglia from the Cerebral Cortex into Subtype Specific Functional Neurons
Heinrich, C., Blum, R., Gascón, S., Masserdotti, G., Tripathi, P., Sánchez, R., Tiedt, S., Schroeder, T., Götz, M., & Berninger, B. (2010) · PLoS Biology · doi:10.1371/journal.pbio.1000373 · Cited by 465
Li, C., Li, K., Wu, D., Chen, Y., Luo, H., Zhao, J., Wang, S.-S., Sun, M.-M., Lu, Y., Zhong, Y., et al. (2015) · Cell Research · doi:10.1038/cr.2015.149 · Cited by 464
Self-citationGenome-scale activation screen identifies a lncRNA locus regulating a gene neighbourhood
Joung, J., Engreitz, J., Konermann, S., Abudayyeh, O. O., Verdine, V. K., Aguet, F., Gootenberg, J. S., Sanjana, N. E., Wright, J. B., Fulco, C. P., et al. (2017) · Nature · doi:10.1038/nature23451 · Cited by 427
Direct neuronal glucose uptake heralds activity-dependent increases in cerebral metabolism
Lundgaard, I., Li, B., Xie, L., Kang, H., Sanggaard, S., Haswell, J. D. R., Sun, W., Goldman, S., Blekot, S., Nielsen, M., et al. (2015) · Nature Communications · doi:10.1038/ncomms7807 · Cited by 381
SHANK3 overexpression causes manic-like behaviour with unique pharmacogenetic properties
Han, K., Holder, J. L., Schaaf, C. P., Lu, H., Chen, H., Kang, H., Tang, J., Wu, Z., Hao, S., Cheung, S. W., et al. (2013) · Nature · doi:10.1038/nature12630 · Cited by 360
Tunable and Multifunctional Eukaryotic Transcription Factors Based on CRISPR/Cas
Farzadfard, F., Perli, S. D., & Lu, T. K. (2013) · ACS Synthetic Biology · doi:10.1021/sb400081r · Cited by 355
Cerebellar modules operate at different frequencies
Zhou, H., Lin, Z., Voges, K., Ju, C., Gao, Z., Bosman, L. W. J., Ruigrok, T. J. H., Hoebeek, F. E., Zeeuw, C. I. D., & Schonewille, M. (2014) · eLife · doi:10.7554/elife.02536 · Cited by 352
Self-citationComplex transcriptional modulation with orthogonal and inducible dCas9 regulators
Gao, Y., Xiong, X., Wong, S. S., Charles, E. J., Lim, W. A., & Qi, L. S. (2016) · Nature Methods · doi:10.1038/nmeth.4042 · Cited by 335
Homology-mediated end joining-based targeted integration using CRISPR/Cas9
Yao, X., Wang, X., Hu, X., Liu, Z., Liu, J., Zhou, H., Shen, X., Yu, W., Huang, Z., Ying, W., et al. (2017) · Cell Research · doi:10.1038/cr.2017.76 · Cited by 332
Self-citationMultiplexable, locus-specific targeting of long RNAs with CRISPR-Display
Shechner, D. M., Hacisuleyman, E., Younger, S. T., & Rinn, J. L. (2015) · Nature Methods · doi:10.1038/nmeth.3433 · Cited by 314
Evaluating cell reprogramming, differentiation and conversion technologies in neuroscience
Mertens, J., Marchetto, M. C., Bardy, C., & Gage, F. H. (2016) · Nature reviews. Neuroscience · doi:10.1038/nrn.2016.46 · Cited by 307
Discovery of stimulation-responsive immune enhancers with CRISPR activation
Simeonov, D. R., Gowen, B. G., Boontanrart, M., Roth, T. L., Gagnon, J. D., Mumbach, M. R., Satpathy, A. T., Lee, Y., Bray, N. L., Chan, A. Y., et al. (2017) · Nature · doi:10.1038/nature23875 · Cited by 297
Orthogonal gene knockout and activation with a catalytically active Cas9 nuclease
Dahlman, J. E., Abudayyeh, O. O., Joung, J., Gootenberg, J. S., Zhang, F., & Konermann, S. (2015) · Nature Biotechnology · doi:10.1038/nbt.3390 · Cited by 266
Ascl1 Converts Dorsal Midbrain Astrocytes into Functional Neurons In Vivo
Liu, Y., Miao, Q., Yuan, J., Han, S., Zhang, P., Li, S., Rao, Z., Zhao, W., Ye, Q., Geng, J., et al. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.3975-14.2015 · Cited by 257
Self-citationAAV-mediated direct in vivo CRISPR screen identifies functional suppressors in glioblastoma
Chow, R. D.-W., Guzman, C. D., Wang, G., Schmidt, F., Youngblood, M. W., Ye, L., Errami, Y., Dong, M. B., Martinez, M. A. Q., Zhang, S., et al. (2017) · Nature Neuroscience · doi:10.1038/nn.4620 · Cited by 240
Black, J. B., Adler, A. F., Wang, H., D’Ippolito, A. M., Hutchinson, H., Reddy, T. E., Pitt, G. S., Leong, K. W., & Gersbach, C. A. (2016) · Cell stem cell · doi:10.1016/j.stem.2016.07.001 · Cited by 223
MECP2 disorders: from the clinic to mice and back
Lombardi, L. M., Baker, S. A., & Zoghbi, H. Y. (2015) · Journal of Clinical Investigation · doi:10.1172/jci78167 · Cited by 221
CRISPR–Cas9-based photoactivatable transcription systems to induce neuronal differentiation
Nihongaki, Y., Furuhata, Y., Otabe, T., Hasegawa, S., Yoshimoto, K., & Sato, M. (2017) · Nature Methods · doi:10.1038/nmeth.4430 · Cited by 175
Direct conversion of astrocytes into neuronal cells by drug cocktail
Cheng, L., Gao, L., Guan, W., Mao, J., Hu, W., Qiu, B., Zhao, J., Yu, Y., & Pei, G. (2015) · Cell Research · doi:10.1038/cr.2015.120 · Cited by 103
Self-citationHuang, M.-G., Huang, T., Xiang, Y., Xie, Z., Chen, Y., Yan, R., Xu, J., & Cheng, L.-P. (2008) · Developmental Biology · doi:10.1016/j.ydbio.2008.06.031 · Cited by 99
Self-citationOu, Z., Niu, X., He, W., Chen, Y., Song, B., Xian, Y., Fan, D., Tang, D., & Sun, X. (2016) · Scientific Reports · doi:10.1038/srep32463 · Cited by 84
MANF regulates hypothalamic control of food intake and body weight
Yang, S., Yang, H., Chang, R., Yin, P., Yang, Y., Yang, W., Huang, S., Gaertig, M. A., Li, S., & Li, X. (2017) · Nature Communications · doi:10.1038/s41467-017-00750-x · Cited by 62
Self-citationSingle and Double Whole-Mount In Situ Hybridization in Red Flour Beetle (Tribolium) EmbryosPreprint
Schinko, J. B., Posnien, N., Kittelmann, S., Koniszewski, N. D. B., & Bucher, G. (2009) · Cold Spring Harbor Protocols · doi:10.1101/pdb.prot5258 · Cited by 61
Dual role of Ski in pancreatic cancer cells: tumor-promoting versus metastasis-suppressive function
Wang, P., Chen, Z., Meng, Z.-Q., Fan, J., Luo, J.-M., Wang, L., Lin, J.-H., Zhou, Z.-H., Chen, H. H., Wang, K., et al. (2009) · Carcinogenesis · doi:10.1093/carcin/bgp154 · Cited by 56
Ivaniutsin, U., Chen, Y., Mason, J. O., Price, D. J., & Pratt, T. (2009) · Neural Development · doi:10.1186/1749-8104-4-3 · Cited by 47
Inner retinal change in a novel rd1-FTL mouse model of retinal degeneration
Greferath, U., Anderson, E. E., Jobling, A. I., Vessey, K. A., Martínez, G., de Iongh, R. U., Kalloniatis, M., & Fletcher, E. L. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00293 · Cited by 16
Anatomical and functional characterization of neuropil in the gracile fasciculus
Ramer, M. S. (2008) · The Journal of Comparative Neurology · doi:10.1002/cne.21785 · Cited by 16
McCracken, J. M., Chalise, P., Briley, S. M., Dennis, K. L., Jiang, L., Duncan, F. E., & Pritchard, M. T. (2017) · Gene Expression · doi:10.3727/105221617x695050 · Cited by 15
Dahlman, J. E., Abudayyeh, O. O., Joung, J., Gootenberg, J. S., Zhang, F., & Konermann, S. (2016) · Nature Biotechnology · doi:10.1038/nbt0416-441a · Cited by 1
Cited by
Sorted by citations
CRISPR/Cas9 therapeutics: progress and prospects
Li, T., Yang, Y., Qi, H., Cui, W., Zhang, L., Fu, X., He, X., Liu, M., Li, P., & Yu, T. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01309-7 · Cited by 824
APOE4/4 is linked to damaging lipid droplets in Alzheimer’s disease microglia
Haney, M. S., Pálovics, R., Munson, C. N., Long, C., Johansson, P. K., Yip, O., Dong, W., Rawat, E., West, E., Schlachetzki, J. C. M., et al. (2024) · Nature · doi:10.1038/s41586-024-07185-7 · Cited by 536
“…indicate that GNE-317 treatment reduced LD concentrations through increasing autophagy, a mechanism which is known to regulate LD concentrations 27–29 ; however, these observations do not conclusively show increased autophagic flux after GNE-317 treatment. were then grown in complete media…”
Engineering the next generation of cell-based therapeutics
Bashor, C. J., Hilton, I. B., Bandukwala, H. S., Smith, D. M., & Omid Veiseh, A. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-022-00476-6 · Cited by 472
Glia-to-Neuron Conversion by CRISPR-CasRx Alleviates Symptoms of Neurological Disease in Mice
Zhou, H., Su, J., Hu, X., Zhou, C., Li, H., Chen, Z., Xiao, Q., Wang, B., Wu, W., Sun, Y., et al. (2020) · Cell · doi:10.1016/j.cell.2020.03.024 · Cited by 437
Self-citationTissue Engineering and Regenerative Medicine: Achievements, Future, and Sustainability in Asia
Han, F., Wang, J., Ding, L., Hu, Y., Li, W., Yuan, Z., Guo, Q., Zhu, C., Yu, L., Wang, H., et al. (2020) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2020.00083 · Cited by 382
Metadata
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
