Modeling xeroderma pigmentosum associated neurological pathologies with patients-derived iPSCs
Year: 2016
Type: article
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.
Source: Protein & Cell
Institutions: Chinese Academy of Sciences, Institute of Biophysics, University of Chinese Academy of Sciences, Foshan University, Salk Institute for Biological Studies, Universidad Católica de Murcia, Beijing Hospital, Peking University Third Hospital, Peking University First Hospital, Institute of Zoology, State Key Laboratory of Stem Cell and Reproductive Biology, Capital Medical University, Beijing Institute for Brain Disorders
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,700
Funders: Leona M. and Harry B. Helmsley Charitable Trust, Consorzio Interuniversitario Biotecnologie, Moxie Foundation, National Natural Science Foundation of China, Chinese Academy of Sciences, Beijing Municipal Science and Technology Commission, National Key Research and Development Program of China, Thousand Young Talents Program of China, National Laboratory of Biomacromolecules
Awards: G1068680877, G1074237133, G117245009, G162887785, G1645120386, G1828425977, G1871641796, G198914242, 人类成年早衰症模型的建立及其分子机制研究, G2475687006, G2685146402, G3101971246, G326723367, G3274609548, G3288158057, G374664538, G563050417, G6067321892, G6559514266, G7046946916, G7407543413, G8842877556, G986533336
OpenAlex ID: W2278964720