Neural Regeneration Research ›› 2024, Vol. 19 ›› Issue (10): 2240-2248.doi: 10.4103/1673-5374.390957

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In situ direct reprogramming of astrocytes to neurons via polypyrimidine tract-binding protein 1 knockdown in a mouse model of ischemic stroke

Meng Yuan1, 2, Yao Tang1, 3, Tianwen Huang4, 5, Lining Ke1, 2, *, En Huang1, 3, *   

  1. 1Key Laboratory of Brain Aging and Neurodegenerative Diseases of Fujian Province, Fujian Medical University, Fuzhou, Fujian Province, China; 2Department of Human Anatomy, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian Province, China; 3Scientific Research Center, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian Province, China; 4Department of Neurology, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China; 5Fujian Key Laboratory of Vascular Aging, Fujian Medical University, Fuzhou, Fujian Province, China
  • Online:2024-10-15 Published:2024-01-29
  • Contact: En Huang, MD, PhD, ehuang0705@fjmu.edu.cn; Lining Ke, MD, PhD, ke-lining@fjmu.edu.cn.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, No. 82071418 and the Natural Science Foundation of Fujian Province, No. 2020J01612 (both to EH).

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Abstract: In situ direct reprogramming technology can directly convert endogenous glial cells into functional neurons in vivo for central nervous system repair. Polypyrimidine tract-binding protein 1 (PTB) knockdown has been shown to reprogram astrocytes to functional neurons in situ. In this study, we used AAV-PHP.eB-GFAP-shPTB to knockdown PTB in a mouse model of ischemic stroke induced by endothelin-1, and investigated the effects of GFAP-shPTB-mediated direct reprogramming to neurons. Our results showed that in the mouse model of ischemic stroke, PTB knockdown effectively reprogrammed GFAP-positive cells to neurons in ischemic foci, restored neural tissue structure, reduced inflammatory response, and improved behavioral function. These findings validate the effectiveness of in situ transdifferentiation of astrocytes, and suggest that the approach may be a promising strategy for stroke treatment.

Key words: astrocyte, in situ direct reprogramming, ischemic stroke, miR-30 based shRNA, neuron, polypyrimidine tract-binding protein 1, transdifferentiation