Modeling xeroderma pigmentosum associated neurological pathologies with patients-derived iPSCs

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

Research output: Contribution to journalArticle

18 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)210-221
Number of pages12
JournalProtein and Cell
Volume7
Issue number3
DOIs
StatePublished - Mar 1 2016
Externally publishedYes

Fingerprint

Xeroderma Pigmentosum
Induced Pluripotent Stem Cells
Pathology
Stem cells
DNA
DNA Damage
Repair
Genes
DNA Repair
Mutation
Neurons
Inborn Genetic Diseases
Neural Stem Cells
Apoptosis
Defects

Keywords

  • disease model
  • iPSC
  • neural stem cell
  • neuron
  • xeroderma pigmentosum

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Drug Discovery
  • Cell Biology

Cite this

Modeling xeroderma pigmentosum associated neurological pathologies with patients-derived iPSCs. / Fu, Lina; Xu, Xiuling; Ren, Ruotong; Wu, Jun; Zhang, Weiqi; Yang, Jiping; Ren, Xiaoqing; Wang, Si; Zhao, Yang; Sun, Liang; Yu, Yang; Wang, Zhaoxia; Yang, Ze; Yuan, Yun; Qiao, Jie; Belmonte, Juan Carlos Izpisua; Qu, Jing; Liu, Guang Hui.

In: Protein and Cell, Vol. 7, No. 3, 01.03.2016, p. 210-221.

Research output: Contribution to journalArticle

Fu, L, Xu, X, Ren, R, Wu, J, Zhang, W, Yang, J, Ren, X, Wang, S, Zhao, Y, Sun, L, Yu, Y, Wang, Z, Yang, Z, Yuan, Y, Qiao, J, Belmonte, JCI, Qu, J & Liu, GH 2016, 'Modeling xeroderma pigmentosum associated neurological pathologies with patients-derived iPSCs', Protein and Cell, vol. 7, no. 3, pp. 210-221. https://doi.org/10.1007/s13238-016-0244-y
Fu, Lina ; Xu, Xiuling ; Ren, Ruotong ; Wu, Jun ; Zhang, Weiqi ; Yang, Jiping ; Ren, Xiaoqing ; Wang, Si ; Zhao, Yang ; Sun, Liang ; Yu, Yang ; Wang, Zhaoxia ; Yang, Ze ; Yuan, Yun ; Qiao, Jie ; Belmonte, Juan Carlos Izpisua ; Qu, Jing ; Liu, Guang Hui. / Modeling xeroderma pigmentosum associated neurological pathologies with patients-derived iPSCs. In: Protein and Cell. 2016 ; Vol. 7, No. 3. pp. 210-221.
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