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 Scopus citations

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

Keywords

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

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Drug Discovery
  • Cell Biology

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  • Cite this

    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, J. C. I., Qu, J., & Liu, G. H. (2016). Modeling xeroderma pigmentosum associated neurological pathologies with patients-derived iPSCs. Protein and Cell, 7(3), 210-221. https://doi.org/10.1007/s13238-016-0244-y