title: Modeling xeroderma pigmentosum associated neurological pathologies with patients-derived iPSCs.
abstract: 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.
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.|University of Chinese Academy of Sciences, Beijing, 100049, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Fu
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Xiuling
authors.initials: X
authors.lastname: Xu
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.|FSU-CAS Innovation Institute, Foshan University, Foshan, 528000, China.
authors.forename: Ruotong
authors.initials: R
authors.lastname: Ren
authors.affiliation: Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA, 92037, USA.|Universidad Católica San Antonio de Murcia (UCAM) Campus de los Jerónimos, Nº 135 Guadalupe 30107, Murcia, Spain.
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.|FSU-CAS Innovation Institute, Foshan University, Foshan, 528000, China.
authors.forename: Weiqi
authors.initials: W
authors.lastname: Zhang
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Jiping
authors.initials: J
authors.lastname: Yang
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Ren
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Si
authors.initials: S
authors.lastname: Wang
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Beijing Hospital of the Ministry of Health, Beijing, 100730, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Gynecology and Obstetrics, Peking University Third Hospital, Beijing, 100191, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Neurology, Peking University First Hospital, Beijing, 100034, China.
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Beijing Hospital of the Ministry of Health, Beijing, 100730, China.
authors.forename: Ze
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Neurology, Peking University First Hospital, Beijing, 100034, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Gynecology and Obstetrics, Peking University Third Hospital, Beijing, 100191, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Qiao
authors.affiliation: Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA, 92037, USA. belmonte@salk.edu.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Izpisua Belmonte
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China. qujing@ioz.ac.cn.
authors.forename: Jing
authors.initials: J
authors.lastname: Qu
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China. ghliu@ibp.ac.cn.|FSU-CAS Innovation Institute, Foshan University, Foshan, 528000, China. ghliu@ibp.ac.cn.|Beijing Institute for Brain Disorders, Capital Medical University, Beijing, 100069, China. ghliu@ibp.ac.cn.|University of Chinese Academy of Sciences, Beijing, 100049, China. ghliu@ibp.ac.cn.
authors.forename: Guang-Hui
authors.initials: GH
authors.lastname: Liu
mesh_terms: D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008954:Models, Biological; D009154:Mutation; D058953:Neural Stem Cells / Q000378:metabolism* / Q000473:pathology; D014983:Xeroderma Pigmentosum / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D004268:DNA-Binding Proteins
keywords: disease model; iPSC; neural stem cell; neuron; xeroderma pigmentosum