中国神经再生研究(英文版) ›› 2015, Vol. 10 ›› Issue (11): 1720-1722.doi: 10.4103/1673-5374.169607

• 观点:神经损伤修复保护与再生 • 上一篇    下一篇

脊髓背根神经撕脱损伤后的感觉再生

  

  • 收稿日期:2015-08-18 出版日期:2015-12-07 发布日期:2015-12-07

Studying neurological disorders using induced pluripotent stem cells and optogenetics

Eunice W.M. Chin, Eyleen L.K. Goh*   

  1. Program in Neuroscience and Behavioral Disorders, Duke-NUS Graduate Medical School, Singapore, Singapore (Chin EW, Goh EL)
    NUS Graduate School for Integrative Singapore, Sciences and Engineering, National University of Singapore, Singapore, Singapore (Chin EW)
    Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore (Goh EL)
    KK Research Center, KK Women’s and Children’s Hospital, Singapore, Singapore (Goh EL)
  • Received:2015-08-18 Online:2015-12-07 Published:2015-12-07
  • Contact: Eyleen L.K. Goh, Ph.D.,eyleen.goh@duke-nus.edu.sg.

摘要:

神经障碍是在人类群体中被研究最广泛的一类疾病,然而,它们也是我们了解最少的疾病之一。基因类型在神经系统疾病的病因学中起到重要作用,尽管大多数这类疾病是多基因类型的,但多基因和基因组变化影响疾病表型的机制仍然没有被很好的理解。因此,传统的疾病建模使用的基因组编辑可以获得所需疾病的基因型技术可能不是最合适能够解决大多数神经障碍的平台。诱导多能干细胞技术的出现为模拟复杂的人类疾病提供了一种变革性的方法。多能干细胞细胞是体细胞,可以通过转录因子被重新编程以恢复其多能性。定向分化是多能干细胞技术的终极目标之一是从多能干细胞获得的分化细胞可用于移植疗法以替代丢失的细胞,也可用于药物筛选,或体外模拟患者特异性疾病。对于神经科学研究来说,人类多能干细胞源性神经元构成了理想的模型系统,可用于神经系统疾病的研究、神经的发育和可塑性研究,而在神经退行性变条件下,它们可以作为以移植为目的疗法的相关细胞来源。

Abstract:

Neurological disorders are amongst the most widely studied human aliments. Yet, they are also one of the most poorly understood. An important role for genotype in the etiology of neurological disorders is suggested, even though most of these disorders are polygenic. For example, in schizophrenia and autism spectrum disorders, there is a 40–60 % concordance rate in monozygotic twins, with 60–90 % heritability. However, the mechanisms by which multiple genes and the genomic variations influence the phenotypes of the disorders remain to be understood. The complexities of the disorders are further compounded by the individual rarity of the genomic variations and their variable penetrance. Thus, conventional disease modeling that makes use of genome editing techniques to attain the desired disease genotype may not be the most suitable platform for tackling most neurological disorders. With the advent of induced pluripotent stem cell (iPSC) technology, there presents a revolutionizing method for modeling complex human disorders. iPSCs are somatic cells that can be reprogrammed through the use of transcription factors to restore pluripotency. Directed differentiation is one of the ultimate goals for iPSC technology. The differentiated cells obtained from iPSCs can be used for transplantation to replace lost cells, for drug screening, or to model patient-specific disease mechanisms in vitro. For neuroscience research, human iPSC-derived neurons make an ideal model system for the study of neurological disorders and the development of neural functionality and plasticity. In the event of neurodegeneration, they can act as a therapeutically relevant source of cells for replacement purposes.