Reprogramming Glial Cells into Functional Neurons for Neuro-regeneration: Challenges and Promise

Abstract

The capacity for neurogenesis in the adult mammalian brain is extremely limited and highly restricted to a few regions, which greatly hampers neuronal regeneration and functional restoration after neuronal loss caused by injury or disease. Meanwhile, transplantation of exogenous neuronal stem cells into the brain encounters several serious issues including immune rejection and the risk of tumorigenesis. Recent discoveries of direct reprogramming of endogenous glial cells into functional neurons have provided new opportunities for adult neuro-regeneration. Here, we extensively review the experimental findings of the direct conversion of glial cells to neurons in vitro and in vivo and discuss the remaining issues and challenges related to the glial subtypes and the specificity and efficiency of direct cell-reprograming, as well as the influence of the microenvironment. Although in situ glial cell reprogramming offers great potential for neuronal repair in the injured or diseased brain, it still needs a large amount of research to pave the way to therapeutic application.

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Acknowledgements

This review was supported by grants from the National Natural Science Foundation of China (32071025), the Beijing Municipal Science & Technology Commission (Z181100001518001), and the Interdisciplinary Research Fund of Beijing Normal University, and the Science and Technology Program of Guangxi (AD21075052), the National Natural Science Foundation of China (31871037 and 32070976), and the Guangxi First-class Discipline Project for Basic Medicine Sciences (GXFCDP-BMS-2018).

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Correspondence to Leping Cheng or Xiaohui Zhang.

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Wang, F., Cheng, L. & Zhang, X. Reprogramming Glial Cells into Functional Neurons for Neuro-regeneration: Challenges and Promise. Neurosci. Bull. (2021). https://doi.org/10.1007/s12264-021-00751-3

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Keywords

  • Direct cell-reprogramming
  • Glial cell-to-neuron conversion
  • Cross-differentiation neuronal regeneration
  • Brain repair