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j.celrep.2018.03.057.pdf | 2.67 MB | Adobe PDF | 見る/開く |
タイトル: | MYC Releases Early Reprogrammed Human Cells from Proliferation Pause via Retinoblastoma Protein Inhibition |
著者: | Rand, Tim A. Sutou, Kenta Tanabe, Koji Jeong, Daeun Nomura, Masaki Kitaoka, Fumiyo Tomoda, Emi Narita, Megumi Nakamura, Michiko Nakamura, Masahiro Watanabe, Akira Rulifson, Eric Yamanaka, Shinya Takahashi, Kazutoshi |
著者名の別形: | 須藤, 健太 野村, 真樹 北岡, 文美代 成田, 恵 中村, 美千子 中村, 正裕 渡辺, 亮 山中, 伸弥 高橋, 和利 |
キーワード: | reprogramming pluripotency induced pluripotent stem cell proliferation senescence immortalization MYC LIN41 post-transcriptional regulation |
発行日: | 10-Apr-2018 |
出版者: | Elsevier BV |
誌名: | Cell Reports |
巻: | 23 |
号: | 2 |
開始ページ: | 361 |
終了ページ: | 375 |
抄録: | Here, we report that MYC rescues early human cells undergoing reprogramming from a proliferation pause induced by OCT3/4, SOX2, and KLF4 (OSK). We identified ESRG as a marker of early reprogramming cells that is expressed as early as day 3 after OSK induction. On day 4, ESRG positive (+) cells converted to a TRA-1-60 (+) intermediate state. These early ESRG (+) or TRA-1-60 (+) cells showed a proliferation pause due to increased p16INK4A and p21 and decreased endogenous MYC caused by OSK. Exogenous MYC did not enhance the appearance of initial reprogramming cells but instead reactivated their proliferation and improved reprogramming efficiency. MYC increased expression of LIN41, which potently suppressed p21 post-transcriptionally. MYC suppressed p16 INK4A. These changes inactivated retinoblastoma protein (RB) and reactivated proliferation. The RB-regulated proliferation pause does not occur in immortalized fibroblasts, leading to high reprogramming efficiency even without exogenous MYC. |
著作権等: | © 2018 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/2433/230952 |
DOI(出版社版): | 10.1016/j.celrep.2018.03.057 |
PubMed ID: | 29641997 |
出現コレクション: | 学術雑誌掲載論文等 |
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