title: Generation of Xeroderma Pigmentosum-A Patient-Derived Induced Pluripotent Stem Cell Line for Use As Future Disease Model.
abstract: Xeroderma pigmentosum group A (XP-A) is a genetic disorder in which there is an abnormality in nucleotide excision repair that causes hypersensitivity to sunlight and multiple skin cancers. The development of central and peripheral neurological disorders not correlated to ultraviolet light exposure is associated with XP-A. The genes responsible for XP-A have been identified and a XPA knockout mouse has been generated. These knockout mice exhibit cutaneous symptoms, but they do not show neurological disorders. The mechanism of pathogenesis of neurological disorders is still unclear and therapeutic methods have not been established. Therefore, we generated XP-A patient-derived human induced pluripotent stem cells (XPA-iPSCs) to produce in vitro models of neurological disorders. We obtained iPSC lines from fibroblasts of two patients carrying different mutations. Drugs screened using XPA-iPSC lines can be helpful for treating XP-A patients in Japan. Additionally, we revealed that these iPSCs have the potential to differentiate into neural lineage cells, including dopaminergic neurons, which decrease in XP-A patients. Our results indicate that expression of the normal XPA gene without mutations is not required for generation of iPSCs and differentiation of iPSCs into neural lineage cells. XPA-iPSCs may become useful models that clarify our understanding of neurological pathogenesis and help to establish therapeutic methods.
authors.affiliation: 1 Tissue Engineering Research Group, Health Research Institute, National Institute of Advanced Industrial Science and Technology (AIST) , Amagasaki, Hyogo 661-0974, Japan .|4 Present address: Department of Otolaryngology, Graduate School of Medicine, Kyoto University , Kyoto 606-8507, Japan .
authors.forename: Hiroe
authors.initials: H
authors.lastname: Ohnishi
authors.affiliation: 2 Functional Biomolecular Research Group, Health Research Institute, National Institute of Advanced Industrial Science and Technology (AIST) , Amagasaki, Hyogo 661-0974, Japan .
authors.forename: Takashi
authors.initials: T
authors.lastname: Kawasaki
authors.affiliation: 3 Stress Signal Research Group, Health Research Institute, National Institute of Advanced Industrial Science and Technology (AIST) , Ikeda, Osaka 563-8577, Japan .
authors.forename: Tomonori
authors.initials: T
authors.lastname: Deguchi
authors.affiliation: 1 Tissue Engineering Research Group, Health Research Institute, National Institute of Advanced Industrial Science and Technology (AIST) , Amagasaki, Hyogo 661-0974, Japan .
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Yuba
mesh_terms: D000818:Animals; D002460:Cell Line; D065150:Cellular Reprogramming; D005347:Fibroblasts / Q000378:metabolism / Q000502:physiology; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism*; D007564:Japan; D051379:Mice; D009154:Mutation; D014983:Xeroderma Pigmentosum / Q000235:genetics / Q000378:metabolism*; D051760:Xeroderma Pigmentosum Group A Protein / Q000235:genetics*
chemical_list: C497314:XPA protein, human; D051760:Xeroderma Pigmentosum Group A Protein