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| 題名: | Distinctive features of single nucleotide alterations in induced pluripotent stem cells with different types of DNA repair deficiency disorders |
| 作者: | 樋口亞紺;Okamura, Kohji;Sakaguchi, Hironari;Sakamoto-Abutani, Rie;Nakanishi, Mahito;Nishimura, Ken;Yamazaki-Inoue, Mayu;Ohtaka, Manami;Periasamy, Vaiyapuri Subbarayan;Alshatwi, Ali Abdullah;Higuchi, Akon;Hanaoka, Kazunori;Nakabayashi, Kazuhiko;Takada, Shuji;Hata, Kenichiro;Toyoda, Masashi;Umezawa, Akihiro |
| 貢獻者: | 工學院化學工程與材料工程學系 |
| 關鍵詞: | 45/23;631/136/1455;692/4017;692/699/4033;Ames test;Ataxia telangiectasia;Cell Line, Tumor;Chromosomes;Deficiency diseases;DNA repair;Double-strand break repair;Drug development;Genes;Genomic instability;Humanities and Social Sciences;Humans;Hypersensitivity;Induced Pluripotent Stem Cells;Induced Pluripotent Stem Cells - cytology;Induced Pluripotent Stem Cells - pathology;Induced Pluripotent Stem Cells - radiation effects;Mammalian cells;Melanoma;Models, Biological;multidisciplinary;Nucleotide excision repair;Pathogenesis;Pluripotency;Point Mutation;Science;Sequence Analysis, DNA;Skin cancer;Skin Neoplasms;Skin Neoplasms - etiology;Skin Neoplasms - genetics;Stem cells;Sunlight;Therapeutic applications;Xeroderma Pigmentosum;Xeroderma Pigmentosum - complications;Xeroderma Pigmentosum - genetics;Xeroderma Pigmentosum - pathology;Xeroderma Pigmentosum Group A Protein;Xeroderma Pigmentosum Group A Protein - genetics |
| 日期: | 2016-05-20 |
| 上傳時間: | 2026-04-21 14:51:55 (UTC+8) |
| 出版者: | Nature Publishing Group;London: Nature Publishing Group |
| 摘要: | 摘要： AbstractDisease-specific induced pluripotent stem cells (iPSCs) have been used as a model to analyze pathogenesis of disease. In this study, we generated iPSCs derived from a fibroblastic cell line of xeroderma pigmentosum (XP) group A (XPA-iPSCs), a rare autosomal recessive hereditary disease in which patients develop skin cancer in the areas of skin exposed to sunlight. XPA-iPSCs exhibited hypersensitivity to ultraviolet exposure and accumulation of single-nucleotide substitutions when compared with ataxia telangiectasia-derived iPSCs that were established in a previous study. However, XPA-iPSCs did not show any chromosomal instability in vitro, i.e. intact chromosomes were maintained. The results were mutually compensating for examining two major sources of mutations, nucleotide excision repair deficiency and double-strand break repair deficiency. Like XP patients, XPA-iPSCs accumulated single-nucleotide substitutions that are associated with malignant melanoma, a manifestation of XP. These results indicate that XPA-iPSCs may serve a monitoring tool (analogous to the Ames test but using mammalian cells) to measure single-nucleotide alterations, and may be a good model to clarify pathogenesis of XP. In addition, XPA-iPSCs may allow us to facilitate development of drugs that delay genetic alteration and decrease hypersensitivity to ultraviolet for therapeutic applications.
其他題名： Sci Rep
出版者： London: Nature Publishing Group
出版日期： 2016-05-20
出處： Scientific Reports, 2016-05, Vol.6 (1), p.26342-, Article 26342
資源來源： Publicly Available Content Database (Proquest)
版權： The Author(s) 2016
版權： Copyright Nature Publishing Group May 2016
版權： Copyright © 2016, Macmillan Publishers Limited 2016 Macmillan Publishers Limited
識別號： ISSN: 2045-2322
識別號： EISSN: 2045-2322
識別號： DOI: 10.1038/srep26342
識別號： PMID: 27197874 |
| 顯示於類別: | [化學工程與材料工程學系 ] 期刊論文
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