Modeling xeroderma pigmentosum associated neurological pathologies with patients-derived iPSCs
Received date: 22 Dec 2015
Accepted date: 29 Dec 2015
Published date: 13 Apr 2016
Copyright
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 patientspecific 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.
Key words: xeroderma pigmentosum; iPSC; disease model; neural stem cell; neuron
Lina Fu , Xiuling Xu , Ruotong Ren , Jun Wu , Weiqi Zhang , Jiping Yang , Xiaoqing Ren , Si Wang , Yang Zhao , Liang Sun , Yang Yu , Zhaoxia Wang , Ze Yang , Yun Yuan , Jie Qiao , Juan Carlos Izpisua Belmonte , Jing Qu , Guang-Hui Liu . Modeling xeroderma pigmentosum associated neurological pathologies with patients-derived iPSCs[J]. Protein & Cell, 2016 , 07(03) : 210 -221 . DOI: 10.1007/s13238-016-0244-y
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