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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  kyouindb  KAKEN_id
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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