1)首都医科大学基础医学院,北京 100069;2)首都医科大学基础医学院生物化学与分子生物学学系,北京 100069;3)首都医科大学基础医学院神经生物学学系,北京 100069
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1)School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China;2)Department of Molecular Biology and Biochemistry, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China;3)Department of Neurobiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China
细胞转分化是通过基因重编程,诱导某种细胞直接转变为另一种细胞,而不经过其他中间状态的过程。神经元丢失是神经系统疾病中常见的病理过程,神经元丢失通常不可逆转,且造成运动、感觉、精神症状。而由于人中枢神经系统神经元再生能力十分有限,仅有部分区域在神经损伤的刺激下能够新生少量神经元。在这样的背景下,将神经胶质细胞(星形胶质细胞、小胶质细胞和少突胶质前体细胞)在神经元丢失处原位转分化为功能性神经元并整合进神经网络的治疗性策略,受到了广泛关注。近年来,学者通过在神经胶质细胞中将神经元命运决定的重要转录因子过表达或敲减等手段,成功实现其向神经元的转分化,取得多项重大进展,但由于目前研究手段的局限性、判断标准的分歧性、结果和结论间较难自洽等问题,部分研究成果的结论仍存在很大的争议。本文系统地回顾了神经胶质细胞转分化为神经元的发现与发展历程,总结了神经胶质细胞转分化为神经元的重要发现,并进行讨论与展望。
Cellular conversion is a process of genetic reprogramming by various methods to induce the direct transformation of one type of cell into another without going through other intermediate states. Neuronal loss is a common pathological process in a variety of neurological disorders, including Parkinson’s disease, Alzheimer’s disease, and stroke. Neuronal loss is usually irreversible and causes motor, sensory, and psychiatric symptoms. Since the human central nervous system has limited capacity for neuronal regeneration, therapeutic strategies that use glial cells (astrocytes, microglia, and oligodendrocyte precursor cells) to transdifferentiate into functional neurons in situ of neuronal loss and integrate them into neural networks have received much attention. In recent years, successful conversion of glia-to-neuron by manipulating the gene expression of key transcription factors in neuronal fate determination in glial cells has been discovered. Nevertheless, there is still some controversy about the scientific validity of some research technologies, the rationality of judgment criteria, and the self-consistency between experimental results and conclusions. This article reviews the discovery and development of glia-to-neuron conversion and takes astrocytes, microglia, and oligodendrocyte progenitor cells as examples to summarize the important findings of glia-to-neuron conversion with discussion and perspective.
赵晓初,罗兆莉,杨菲,李纤.综述与专论: 神经胶质细胞转分化为神经元的研究进展[J].生物化学与生物物理进展,2022,49(11):2087-2098
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