Modeling xeroderma pigmentosum associated neurological pathologies with patients-derived iPSCs

分类： 生物学 >> 生物物理学 >> 细胞生物学 提交时间： 2016-05-05

Fu, Lina Xu, Xiuling Ren, Ruotong Zhang, Weiqi Yang, Jiping Ren, Xiaoqing Wang, Si Zhao, Yang Liu, Guang-Hui Ren, Ruotong Zhang, Weiqi Liu, Guang-Hui Qu, Jing Wu, Jun Belmonte, Juan Carlos Izpisua Wu, Jun Sun, Liang Yang, Ze Yu, Yang Qiao, Jie

摘要： Xeroderma pigmentosum (XP) is a group of genetic disorders caused by mutations of XP-associated genes, resulting in impairment of DNA repair. XP patients frequently exhibit neurological degeneration, but the underlying mechanism is unknown, in part due to lack of proper disease models. Here, we generated patient-specific induced pluripotent stem cells (iPSCs) harboring mutations in five different XP genes including XPA, XPB, XPC, XPG, and XPV. These iPSCs were further differentiated to neural cells, and their susceptibility to DNA damage stress was investigated. Mutation of XPA in either neural stem cells (NSCs) or neurons resulted in severe DNA damage repair defects, and these neural cells with mutant XPA were hyper-sensitive to DNA damage-induced apoptosis. Thus, XP-mutant neural cells represent valuable tools to clarify the molecular mechanisms of neurological abnormalities in the XP patients.

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