Modeling xeroderma pigmentosum associated neurological pathologies with patients-derived iPSCs

作     者：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 

作者机构：National Laboratory of Biomacromolecules Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China FSU-CAS Innovation Institute Foshan University Foshan 528000 China State Key Laboratory of Stem Cell and Reproductive Biology Institute of Zoology Chinese Academy of Sciences Beijing 100101 China Gene Expression Laboratory Salk Institute for Biological Studies 10010 North Torrey Pines Road La Jolla CA 92037 USA Universidad Cato1ica San Antonio de Murcia (UCAIVI) Campus de los Jer6nimos N° 135 Guadalupe 30107 Murcia Spain Beijing Hospital of the Ministry of Health Beijing 100730 China Department of Gynecology and Obstetrics Peking University Third Hospital Beijing 100191 China Department of Neurology Peking University First Hospital Beijing 100034 China Beijing Institute for Brain Disorders Capital Medical University Beijing 100069 China University of Chinese Academy of Sciences Beijing 100049 China 

出 版 物：《Protein & Cell》 (蛋白质与细胞（英文版）)

年 卷 期：2016年第7卷第3期

页      面：210-221页

核心收录：

学科分类：0710[理学-生物学] 0831[工学-生物医学工程（可授工学、理学、医学学位）] 1007[医学-药学(可授医学、理学学位)] 1002[医学-临床医学] 07[理学] 071006[理学-神经生物学] 0703[理学-化学] 0836[工学-生物工程] 

基　　金：This work was supported by National Basic Research Program (973 Program) (Nos. 2015CB964800 and 2014CB910503), the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA01020312), National High Technology Research and Development Program of China (2015AA020307), National Natural Science Foundation of China (Grant Nos. 81330008, 31222039, 31201111, 81371342, 81300261, 81300677, 81271266, 81471414, 81422017, and 81401159), Beijing Natural Science Foundation (7141005 5142016), Program of Beijing Municipal Science and Technology Commission (Z151100003915072), Key Research Program of the Chinese Academy of Sciences (KJZDEW-TZ-L05), the Thousand Young Talents program of China, National Laboratory of Biomacromolecules (012kf02, 2013kf05, 2013kf11, 2014kf02, 2015kfl 0). J.C.I.B. was supported by UCAM, the G. Harold and Leila Y. Mathers Charitable Foundation, the Leona M. and Harry B. Helmsley Charitable Trust (2012-PG-MED002) and the Moxie Foundation 

主　　题：xeroderma pigmentosum iPSC disease model neural stem cell. neuron 

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 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 clari the molecular mechanisms of neurological abnormalities in the XP patients.