中国神经再生研究(英文版) ›› 2024, Vol. 19 ›› Issue (on line): 1-15.

• •    下一篇

Characteristic changes in astrocyte properties during astrocyte-to-neuron conversion induced by NeuroD1/Ascl1/Dlx2

  

  • 出版日期:2024-01-01 发布日期:2024-05-11

Qing He#, Zhen Wang#, Yuchen Wang, Mengjie Zhu, Zhile Liang, Kanghong Zhang, Yuge Xu, Gong Chen*   

  1. GHM Institute of CNS Regeneration, Jinan University, Guangzhou, Guangdong Province, China
  • Online:2024-01-01 Published:2024-05-11
  • Contact: Gong Chen, PhD, gongchen@jnu.edu.cn.
  • Supported by:
    This study was supported by the Key Project of Guangzhou City, No. 202206060002; Science and Technology Project of Guangdong Province, No. 2018B030332001; Guangdong Provincial Pearl River Project, No. 2021ZT09Y552 (all to GC).

摘要: https://orcid.org/0000-0002-1857-3670 (Gong Chen)

Abstract: Direct in vivo conversion of astrocytes into functional new neurons induced by neural transcription factors has been recognized as a potential new therapeutic intervention for neural injury and degenerative disorders. However, a few recent studies have claimed that neural transcription factors cannot convert astrocytes into neurons, attributing the converted neurons to pre-existing neurons mis-expressing transgenes. In this study, we overexpressed three distinct neural transcription factors––NeuroD1, Ascl1, and Dlx2––in reactive astrocytes in mouse cortices subjected to stab injury, resulting in a series of significant changes in the astrocytes’ properties. Initially, the three neural transcription factors were exclusively expressed in the nuclei of astrocytes. Over time, however, these astrocytes gradually adopted neuronal morphology, and the neural transcription factors was gradually observed in the nuclei of neuron-like cells instead of astrocytes. Furthermore, we noted that transcription factor-infected astrocytes showed a progressive decrease in the expression of astrocytic markers AQP4 (astrocyte endfeet signal), CX43 (gap junction signal), and S100β. Importantly, none of these changes could be attributed to transgene leakage into pre-existing neurons. Therefore, our findings suggest that neural transcription factors such as NeuroD1, Ascl1, and Dlx2 can effectively convert reactive astrocytes into neurons in the adult mammalian brain.

Key words: aquaporin-4, Ascl1, astrocyte, cortex, Dlx2, gap junction, glia-to-neuron conversion, neural regeneration, NeuroD1, reprogramming