Modeling xeroderma pigmentosum associated neurological pathologies with patients-derived iPSCs
Protein & Cell
;
(12): 210-221, 2016.
Artigo
em Inglês
| 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.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Patologia
/
Xeroderma Pigmentoso
/
Dano ao DNA
/
Proteínas de Ligação a DNA
/
Reparo do DNA
/
Células-Tronco Pluripotentes Induzidas
/
Células-Tronco Neurais
/
Genética
/
Metabolismo
/
Modelos Biológicos
Limite:
Feminino
/
Humanos
/
Masculino
Idioma:
Inglês
Revista:
Protein & Cell
Ano de publicação:
2016
Tipo de documento:
Artigo
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