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

Fengchao Wang1 • Leping Cheng2,3,4 • Xiaohui Zhang1

 

1 State Key Laboratory of Cognitive Neuroscience and Learning, IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing 100875, China

2 Key Laboratory of Longevity and Aging-related Diseases of Chinese Ministry of Education, Guangxi-ASEAN Collaborative Innovation Center for Major Disease Prevention and Treatment, and Guangxi Key Laboratory of Regenerative Medicine, Center for Translational Medicine, Guangxi Medical University, Nanning 530021, China

3 Department of Cell Biology and Genetics, School of Basic Medical Sciences, Guangxi Medical University, Nanning 530021, China

4 Guangxi Health Commission Key Laboratory of Basic Research on Brain Function and Disease, Guangxi Medical University, Nanning 530021, China

 

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.

 

Keywords

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

 

 

[SpringerLink]