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j.stemcr.2019.04.008.pdf | 4.39 MB | Adobe PDF | 見る/開く |
タイトル: | De Novo DNA Methylation at Imprinted Loci during Reprogramming into Naive and Primed Pluripotency |
著者: | Yagi, Masaki Kabata, Mio Ukai, Tomoyo Ohta, Sho Tanaka, Akito Shimada, Yui Sugimoto, Michihiko Araki, Kimi Okita, Keisuke https://orcid.org/0000-0001-5806-1090 (unconfirmed) Woltjen, Knut https://orcid.org/0000-0003-2293-1183 (unconfirmed) Hochedlinger, Konrad Yamamoto, Takuya https://orcid.org/0000-0002-0022-3947 (unconfirmed) Yamada, Yasuhiro |
著者名の別形: | 八木, 正樹 蒲田, 未央 鵜飼, 智代 太田, 翔 田中, 彰人 島田, 由衣 杉本, 道彦 荒木, 喜美 沖田, 圭介 ウォルツェン, クヌート 山本, 拓也 山田, 泰広 |
キーワード: | pluripotent stem cells naive and primed pluripotency reprogramming pediatric cancers DNA methylation genomic imprinting CpG islands Dnmt3a |
発行日: | 14-May-2019 |
出版者: | Elsevier BV |
誌名: | Stem Cell Reports |
巻: | 12 |
号: | 5 |
開始ページ: | 1113 |
終了ページ: | 1128 |
抄録: | CpG islands (CGIs) including those at imprinting control regions (ICRs) are protected from de novo methylation in somatic cells. However, many cancers often exhibit CGI hypermethylation, implying that the machinery is impaired in cancer cells. Here, we conducted a comprehensive analysis of CGI methylation during somatic cell reprogramming. Although most CGIs remain hypomethylated, a small subset of CGIs, particularly at several ICRs, was often de novo methylated in reprogrammed pluripotent stem cells (PSCs). Such de novo ICR methylation was linked with the silencing of reprogramming factors, which occurs at a late stage of reprogramming. The ICR-preferred CGI hypermethylation was similarly observed in human PSCs. Mechanistically, ablation of Dnmt3a prevented PSCs from de novo ICR methylation. Notably, the ICR-preferred CGI hypermethylation was observed in pediatric cancers, while adult cancers exhibit genome-wide CGI hypermethylation. These results may have important implications in the pathogenesis of pediatric cancers and the application of PSCs. |
記述: | iPS細胞樹立時に起こりうる異常の同定とその回避方法の開発 --安全な細胞運命制御技術の開発に向けて--. 京都大学プレスリリース. 2019-05-21. |
著作権等: | © 2019 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
URI: | http://hdl.handle.net/2433/241550 |
DOI(出版社版): | 10.1016/j.stemcr.2019.04.008 |
PubMed ID: | 31056481 |
関連リンク: | https://www.kyoto-u.ac.jp/ja/research-news/2019-05-21 |
出現コレクション: | 学術雑誌掲載論文等 |
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