Protein & Cell >

2016 , Vol. 07 >Issue 03: 210 - 221

DOI: https://doi.org/10.1007/s13238-016-0244-y

RESEARCH ARTICLE

Modeling xeroderma pigmentosum associated neurological pathologies with patients-derived iPSCs

  • Lina Fu 1,10 ,
  • Xiuling Xu 1 ,
  • Ruotong Ren 1,2 ,
  • Jun Wu 4,5 ,
  • Weiqi Zhang 1,2 ,
  • Jiping Yang 1 ,
  • Xiaoqing Ren 1 ,
  • Si Wang 1 ,
  • Yang Zhao 1 ,
  • Liang Sun 6 ,
  • Yang Yu 7 ,
  • Zhaoxia Wang 8 ,
  • Ze Yang 6 ,
  • Yun Yuan 8 ,
  • Jie Qiao 7 ,
  • Juan Carlos Izpisua Belmonte , 4 ,
  • Jing Qu , 3 ,
  • Guang-Hui Liu , 1,2,9,10
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  • 1. National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
  • 2. FSU-CAS Innovation Institute, Foshan University, Foshan 528000, China
  • 3. State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
  • 4. Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA
  • 5. Universidad Católica San Antonio de Murcia (UCAM) Campus de los Jerónimos, No 135 Guadalupe 30107, Murcia, Spain
  • 6. Beijing Hospital of the Ministry of Health, Beijing 100730, China
  • 7. Department of Gynecology and Obstetrics, Peking University Third Hospital, Beijing 100191, China
  • 8. Department of Neurology, Peking University First Hospital, Beijing 100034, China
  • 9. Beijing Institute for Brain Disorders, Capital Medical University, Beijing 100069, China
  • 10. University of Chinese Academy of Sciences, Beijing 100049, China

Received date: 22 Dec 2015

Accepted date: 29 Dec 2015

Published date: 13 Apr 2016

Copyright

2014 This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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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 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

Cite this article

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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