Department of Pathology, and Taub Institute, Columbia University, Black Building 1208, 650 West 168th Street, New York, NY 10032, USA.
Neuron. 2013 Jun 19;78(6):957-69. doi: 10.1016/j.neuron.2013.06.002.
Epigenetic reprogramming of adult human somatic cells to alternative fates, such as the conversion of human skin fibroblasts to induced pluripotency stem cells (iPSC), has enabled the generation of novel cellular models of CNS disorders. Cell reprogramming models appear particularly promising in the context of human neurological disorders of aging such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), for which animal models may not recapitulate key aspects of disease pathology. In addition, recent developments in reprogramming technology have allowed for more selective cell fate interconversion events, as from skin fibroblasts directly to diverse induced neuron (iN) subtypes. Challenges to human reprogramming-based cell models of disease are the heterogeneity of the human population and the extended temporal course of these disorders. A major goal is the accurate modeling of common nonfamilial "sporadic" forms of brain disorders.
成年人类体体细胞向其他命运的表观遗传重编程，如将人类皮肤成纤维细胞诱导为多能干细胞（iPSC），使中枢神经系统疾病的新型细胞模型得以产生。在与衰老相关的人类神经疾病（如阿尔茨海默病（AD）、帕金森病（PD）和肌萎缩性侧索硬化症（ALS））的背景下，细胞重编程模型似乎特别有前景，因为动物模型可能无法重现疾病病理的关键方面。此外，最近的重编程技术的发展使得更具选择性的细胞命运转化事件成为可能，例如直接将皮肤成纤维细胞转化为多种诱导神经元（iN）亚型。基于人类重编程的疾病细胞模型的挑战是人类群体的异质性和这些疾病的长时间过程。一个主要目标是准确模拟常见的非家族性“散发性”脑疾病。
