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Cited by 437CRISPR and Genetic EngineeringRetinal Development and DisordersPluripotent Stem Cells Research

Glia-to-Neuron Conversion by CRISPR-CasRx Alleviates Symptoms of Neurological Disease in Mice

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Zhou, Haibo, Su, Jinlin, Hu, Xinde, Zhou, Changyang, Li, He, Chen, Zhaorong, Xiao, Qingquan, Wang, Bo +14 more·2020·Cell
DOI 10.1016/j.cell.2020.03.024
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Abstract

Conversion of glial cells into functional neurons represents a potential therapeutic approach for replenishing neuronal loss associated with neurodegenerative diseases and brain injury. Previous attempts in this area using expression of transcription factors were hindered by the low conversion efficiency and failure of generating desired neuronal types in vivo. Here, we report that downregulation of a single RNA-binding protein, polypyrimidine tract-binding protein 1 (Ptbp1), using in vivo viral delivery of a recently developed RNA-targeting CRISPR system CasRx, resulted in the conversion of Müller glia into retinal ganglion cells (RGCs) with a high efficiency, leading to the alleviation of disease symptoms associated with RGC loss. Furthermore, this approach also induced neurons with dopaminergic features in the striatum and alleviated motor defects in a Parkinson's disease mouse model. Thus, glia-to-neuron conversion by CasRx-mediated Ptbp1 knockdown represents a promising in vivo genetic approach for treating a variety of disorders due to neuronal loss.

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  • Early studies reported that suppressing PTBP1 in astrocytes or other glia could initiate neuronal transcriptional programs and produce cells resembling functional neurons in models of Parkinson's disease and retinal injury.

    “Early studies reported that suppressing PTBP1 in astrocytes or other glia could initiate neuronal transcriptional programs and produce cells resembling functional neurons in models of Parkinson’s disease and retinal injury, sparking strong enthusiasm for PTBP1 as a single-factor reprogramming node.”

    From Reverse the progression of Alzheimer’s disease through Nano-ERASER-based adult neuroregeneration (2026) · cites this paper as [14]

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Cited by

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Authors
Zhou, H., Su, J., Hu, X., Zhou, C., Li, H., Chen, Z., Xiao, Q., Wang, B., Wu, W., Sun, Y., Zhou, Y., Tang, C., Liu, F., Wang, L., Feng, C., Liu, M., Li, S., Zhang, Y., Xu, H., Yao, H., Shi, L., & Yang, H.
Affiliations
Chinese Academy of Sciences (CN)
Corresponding author
  • Zhou, Haibo
  • Yang, Hui
ORCID
Venue
Cell
Publisher
Elsevier BV
Published
2020-04
Volume
181
Issue
3
Pages
590-603.e16
ISSN
0092-8674 (ISSN-L)
DOI
10.1016/j.cell.2020.03.024
OpenAlex
W3015411398
Cited by
437
References
2
Citations by year
2026: 36 · 2025: 55 · 2024: 59 · 2023: 78 · 2022: 90 · 2021: 87 · 2020: 32
FWCI
23.28
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Chinese Academy of Sciences
  • Science and Technology Commission of Shanghai Municipality
  • National Natural Science Foundation of China
  • Ministry of Science and Technology of the People's Republic of China
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
Keywords
glia-to-neuron conversion, PTBP1, Müller cells, retinal ganglion cells, retinal degeneration, Parkinson's disease, dopaminergic neurons, striatum, neuronal loss, neurodegenerative disease treatment
MeSH terms
Animals, Cell Differentiation, Cells, Cultured, Disease Models, Animal, Dopamine, Gene Expression Regulation, Male, Mice, Inbred C57BL, Nervous System Diseases, Neuroglia, Neurons, Parkinson Disease, Retinal Ganglion Cells, Heterogeneous-Nuclear Ribonucleoproteins, Polypyrimidine Tract-Binding Protein, Mice, Neurogenesis, Clustered Regularly Interspaced Short Palindromic Repeats, CRISPR-Cas Systems

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