State Key Laboratory of Cognitive Neuroscience and Learning, IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, 100875, China.
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.
Neurosci Bull. 2021 Nov;37(11):1625-1636. doi: 10.1007/s12264-021-00751-3. Epub 2021 Jul 20.
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.
成年哺乳动物大脑中的神经发生能力极其有限，并且高度局限于少数几个区域，这极大地阻碍了神经元在损伤或疾病导致的神经元损失后的再生和功能恢复。同时，将外源性神经元干细胞移植到大脑中会遇到一些严重的问题，包括免疫排斥和致癌风险。最近发现的内源性神经胶质细胞直接重编程为功能性神经元为成年神经再生提供了新的机会。在这里，我们广泛综述了体外和体内将神经胶质细胞直接转化为神经元的实验发现，并讨论了与神经胶质亚型以及直接细胞重编程的特异性和效率相关的剩余问题和挑战，以及微环境的影响。尽管原位神经胶质细胞重编程为损伤或患病大脑中的神经元修复提供了巨大的潜力，但它仍然需要大量的研究来为治疗应用铺平道路。
