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タイトル: | Base-Resolution Methylome of Retinal Pigment Epithelial Cells Used in the First Trial of Human Induced Pluripotent Stem Cell-Based Autologous Transplantation |
著者: | Araki, Hiromitsu Miura, Fumihito Watanabe, Akira Morinaga, Chikako Kitaoka, Fumiyo Kitano, Yuko Sakai, Noriko Shibata, Yumiko Terada, Motoki Goto, So Yamanaka, Shinya Takahashi, Masayo Ito, Takashi |
著者名の別形: | 渡辺, 亮 北岡, 文美代 山中, 伸弥 |
キーワード: | age-related macular degeneration patient-derived iPSCs DNA methylation whole-genome bisulfite sequencing |
発行日: | 8-Oct-2019 |
出版者: | Elsevier BV |
誌名: | Stem Cell Reports |
巻: | 13 |
号: | 4 |
開始ページ: | 761 |
終了ページ: | 774 |
抄録: | The first-in-human trial of induced pluripotent stem cell (iPSC)-based autologous transplantation was successfully performed on a female patient with age-related macular degeneration. Here we delineated the base-resolution methylome of the iPSC-derived retinal pigment epithelium (iRPE) used in this trial. The methylome of iRPE closely resembled that of native RPE (nRPE), although partially methylated domains (PMDs) emerged in iRPE but not nRPE. Most differentially methylated regions between iRPE and nRPE appeared to originate from (de)methylation errors during differentiation, whereas errors at reprogramming resulted in aberrant genomic imprinting and X chromosome reactivation. Moreover, non-CpG methylation was prominent in nRPE but not iRPE. Intriguingly, xenotransplantation to mouse remodeled the iRPE methylome to demethylate a subset of suppressed genes and accumulate non-CpG methylation, but failed to resolve PMDs and hypermethylated CpG islands. Although the impacts of these alterations remain elusive, our findings should provide a useful guide for methylome analyses of other iPSC-derived cells. |
著作権等: | This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
URI: | http://hdl.handle.net/2433/244381 |
DOI(出版社版): | 10.1016/j.stemcr.2019.08.014 |
PubMed ID: | 31564644 |
出現コレクション: | 学術雑誌掲載論文等 |
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