Modeling xeroderma pigmentosum associated neurological pathologies with patients-derived iPSCs.
10.1007/s13238-016-0244-y
- Author:
Lina FU
1
;
Xiuling XU
1
;
Ruotong REN
1
;
Jun WU
2
;
Weiqi ZHANG
1
;
Jiping YANG
1
;
Xiaoqing REN
1
;
Si WANG
1
;
Yang ZHAO
1
;
Liang SUN
3
;
Yang YU
4
;
Zhaoxia WANG
5
;
Ze YANG
3
;
Yun YUAN
5
;
Jie QIAO
4
;
Juan Carlos IZPISUA BELMONTE
6
;
Jing QU
7
;
Guang-Hui LIU
8
Author Information
1. National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
2. Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA, 92037, USA.
3. Beijing Hospital of the Ministry of Health, Beijing, 100730, China.
4. Department of Gynecology and Obstetrics, Peking University Third Hospital, Beijing, 100191, China.
5. Department of Neurology, Peking University First Hospital, Beijing, 100034, China.
6. Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA, 92037, USA. belmonte@salk.edu.
7. State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China. qujing@ioz.ac.cn.
8. National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China. ghliu@ibp.ac.cn.
- Publication Type:Journal Article
- Keywords:
disease model;
iPSC;
neural stem cell;
neuron;
xeroderma pigmentosum
- MeSH:
DNA Damage;
DNA Repair;
DNA-Binding Proteins;
genetics;
metabolism;
Female;
Humans;
Induced Pluripotent Stem Cells;
metabolism;
pathology;
Male;
Models, Biological;
Mutation;
Neural Stem Cells;
metabolism;
pathology;
Xeroderma Pigmentosum;
genetics;
metabolism;
pathology
- From:
Protein & Cell
2016;7(3):210-221
- CountryChina
- Language:English
-
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.
