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Dead Cas(t) light on new life: CRISPRa-mediated reprogramming of somatic cells into neurons

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Abstract

Overexpression of exogenous lineage-specific transcription factors could directly induce terminally differentiated somatic cells into target cell types. However, the low conversion efficiency and the concern about introducing exogenous genes limit the clinical application. With the rapid progress in genome editing, the application of CRISPR/dCas9 has been expanding rapidly, including converting somatic cells into other types of cells in vivo and in vitro. Using the CRISPR/dCas9 system, direct neuronal reprogramming could be achieved by activating endogenous genes. Here, we will discuss the latest progress, new insights, and future challenges of the application of the dCas9 system in direct neuronal reprogramming.

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Acknowledgements

We thank the members of Zhang’s laboratory for the constructive discussions.

Funding

This work was supported by the National Natural Science Foundation of China 81471283 (B. Z.) and the National Natural Science Foundation of China 82072795 (F. W.).

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Authors and Affiliations

  1. Wuhan Institute of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan, 430056, China

    Meiling Zhou, Yu Cao & Xiji Shu

  2. Department of Physiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Ming Sui & Bin Zhang

  3. Department of Neurosurgery, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Feng Wan

  4. The Institute for Brain Research, Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, 430030, China

    Bin Zhang

  5. Hubei Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation, Huazhong University of Science and Technology, Wuhan, 430030, China

    Bin Zhang

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  1. Meiling Zhou
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  5. Feng Wan
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The manuscript was drafted by MZ. YC, MS, XS, FW, and BZ edited the manuscript. All authors have read and approved the final manuscript.

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Correspondence to Feng Wan or Bin Zhang.

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Zhou, M., Cao, Y., Sui, M. et al. Dead Cas(t) light on new life: CRISPRa-mediated reprogramming of somatic cells into neurons. Cell. Mol. Life Sci. 79, 315 (2022). https://doi.org/10.1007/s00018-022-04324-z

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