Direct Conversion of Somatic Cells into Induced Neurons
Direct Conversion of Somatic Cells into Induced Neurons
复制标题
体细胞直接转化为诱导神经元
DOI：
10.1007/s12035-016-0350-0
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发表时间：
2018-01-01
影响因子：
5.1
通讯作者：
Yang, Hao
中科院分区：
文献类型：
--
作者：
An, Na;Xu, Huiming;Yang, Hao
由于创伤或疾病（包括阿尔茨海默氏症、帕金森氏症、亨廷顿氏病、中风以及脑和脊髓的创伤性损伤），中枢神经系统（CNS）中神经元的进行性损失和变性通常会对生活质量产生破坏性影响。目前的治疗策略，包括药物输送，手术，电刺激和细胞为基础的组织工程方法进行了描述。然而，除了基于细胞的治疗之外，其他尝试在改善临床结果方面受到限制。最近，干细胞和神经干细胞（NSC）特别是治疗已被提出作为一个有吸引力的和有前途的策略，再生医学由于其独特的生物学属性，如引起神经细胞谱系承诺根据神经发育。然而，干细胞策略仍面临许多挑战，包括伦理问题、肿瘤形成和移植排斥。因此，寻求更合适的方法，如直接重编程或谱系重编程是至关重要的。与诱导多能干细胞（iPSC）和胚胎干细胞（ESC）相比，体细胞的直接谱系重编程以产生诱导神经元（iN）而不经历多能状态仍然具有几个优点，例如诱导周期短、转分化效率高、没有伦理问题和肿瘤形成的风险。在这些优势的基础上，细胞重编程将为治疗性细胞替代、疾病模型建立、药物筛选和个性化医疗带来巨大希望。本文系统地综述了近年来体细胞谱系重编程为iNs的研究进展，包括新的重编程因子的发现、潜在的分子机制和存在的问题，以及未来面临的主要挑战。
The progressive loss and degeneration of neurons in the central nervous system (CNS), as a result of traumas or diseases including Alzheimer's, Parkinson's, Huntington's disease, stroke, and traumatic injury to the brain and spinal cord, can usually have devastating effects on quality of life. The current strategies available for treatments are described including drug delivery, surgery, electrical stimulation, and cell-based tissue engineering approaches. However, apart from cell-based therapy, other attempts are limited in improving clinical outcomes. Recently, stem cell and neural stem cell (NSC) in particular therapy has been proposed as an attractive and promising strategy for regenerative medicine due to their unique biological attributes, such as giving rise to neuronal lineage commitment in accordance with the neural development. Nevertheless, stem cell strategy still faces numerous challenges, including ethical issue, tumor formation, and graft rejection. Thus, seeking a more appropriate approach like direct reprogramming or lineage reprogramming is critical. Compared to induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs), direct lineage reprogramming of somatic cells to generate induced neurons (iNs) without undergoing a state of pluripotent still has several advantages such as short induction cycle, high transdifferentiation efficiency, no ethical concerns, and risk of neoplasia. On the basis of these advantages, cell reprogramming will hold great promise for therapeutic cell replacement, disease modeling establishment, drug screening, and personalized medicine. Here, we systematically review recent advances in somatic lineage reprogramming into iNs, including the identification of novel reprogramming factors, the underlying molecular mechanisms and the concerns exist, as well as the major challenges in the future.