Modeling xeroderma pigmentosum associated neurological pathologies with patients-derived iPSCs
Protein & Cell
;
(12): 210-221, 2016.
Article
in English
| WPRIM
| ID: wpr-757146
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Pathology
/
Xeroderma Pigmentosum
/
DNA Damage
/
DNA-Binding Proteins
/
DNA Repair
/
Induced Pluripotent Stem Cells
/
Neural Stem Cells
/
Genetics
/
Metabolism
/
Models, Biological
Limits:
Female
/
Humans
/
Male
Language:
English
Journal:
Protein & Cell
Year:
2016
Type:
Article
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