《生命科学》 2026, 38(7): 1301-1313
NG2胶质细胞重编程的研究进展
摘 要：
近年来，胶质细胞重编程已成为一种潜在的细胞替代治疗策略。NG2胶质细胞重编程通过将损伤区域邻近 的内源性NG2胶质细胞直接转分化为神经元，不仅可规避外源性细胞移植引发的免疫排斥，还能通过重塑微环境稳 态显著促进神经修复，展现出良好的应用前景。NG2胶质细胞重编程受多种因素影响或调控，包括损伤相关的炎症 反应、硫酸软骨素蛋白聚糖（CSPG）、小分子化合物，以及小胶质细胞和星形胶质细胞等的相互作用。深入理解这些 调控因素，对于提高重编程效率及发现新的重编程因子具有重要意义。本综述系统回顾了NG2胶质细胞重编程为 神经元的研究进展，总结了关键转录因子及微环境调控机制，并对当前重编程过程中存在的主要问题进行了探讨与 展望，旨在为该技术的临床转化提供理论依据与创新思路。
通讯作者：罗 靖 , Email:2292940670@qq.com
Abstract:
This review systematically synthesizes the advancements in research concerning the reprogramming of NG2 glial cells into functional neurons, with an emphasis on elucidating the principal transcriptional regulators, microenvironmental modulators, and mechanisms of cellular interaction involved. It seeks to deliver a comprehensive analysis of the molecular foundations of this process and to prospectively assess its translational potential and the associated challenges within the context of neural injury repair and neurological disease therapy. (1) First, this review initially delineates the fundamental transcription factors responsible for the reprogramming of NG2 glial cells, specifically NeuroD1, Sox2, Dlx2, Ascl1, Lmx1a, and Nurr1. These transcription factors may operate independently or synergistically to facilitate the transformation of NG2 glia into either glutamatergic or GABAergic neurons across a range of injury models, including spinal cord injury, cortical stab wound, and Alzheimer′s disease. Importantly, Sox2 and NeuroD1 have been recognized as particularly effective inducers, promoting not only neuronal differentiation but also axonal regeneration and subsequent functional recovery. (2) Second, we investigate the pivotal regulatory functions of injury microenvironment in the reprogramming process. It explores how inflammatory responses, chondroitin sulfate proteoglycans (CSPGs), epigenetic barriers, and complex interactions with other glial cells—specifically microglia and astrocytes—collectively regulate or influence the reprogramming fate of NG2 glia. For example, while heightened inflammation generally reduces reprogramming efficiency, NG2 glia can counteract this effect by secreting anti-inflammatory factors such as TGF-β and MHC I. CSPGs serve as a physico-chemical barrier that hinders NG2 glial reprogramming; however, inhibitory strategies like the administration of intracellular sigma peptide (ISP) can partially overcome this obstacle. Microglia influence the state of NG2 cells through the release of cytokines and other signaling molecules, whereas astrocytes may compete for reprogramming factors and contribute to a scar-associated microenvironment, thereby indirectly impacting the neuronal differentiation pathway of NG2 glia. In comparison to astrocyte-based reprogramming, NG2 glia present distinct advantages, such as increased proliferative capacity, enhanced chromatin plasticity, superior synaptic integration potential, and a more favorable safety profile regarding blood-brain barrier integrity. Collectively, these characteristics position NG2 glial cells as a highly promising endogenous source for neural repair strategies. (3) Furthermore, this review synthesizes recent advancements in understanding the role of small-molecule compounds and their epigenetic regulatory mechanisms in modulating NG2 glial reprogramming. Notably, small molecules, particularly histone deacetylase (HDAC) inhibitors, exhibit significant potential to enhance reprogramming efficiency by remodeling chromatin accessibility and facilitating the binding of transcription factors to their target genomic regions. While preclinical studies have shown promise, the clinical application of NG2 glial cell reprogramming is hindered by several critical challenges. These challenges include the considerable differences between in vitro and in vivo microenvironments, the oncogenic potential associated with viral vector integration, and the necessity for precise regulation of neuronal subtype specification and functional circuit integration. To overcome these obstacles and further the field, we propose the following recommendations: (1) Develop and implement non-integrating delivery systems, such as episomal vectors or virus-like particles; (2) Combine small molecules with transcription factors to develop safer ″all-chemical″ reprogramming strategies; (3) Employ single-cell multi-omics technologies to dynamically map the epigenetic and transcriptional landscapes during the reprogramming process.
Communication Author：LUO Jing , Email:2292940670@qq.com
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