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j.bbrc.2018.11.164.pdf | 2.41 MB | Adobe PDF | 見る/開く |
タイトル: | AMPK activators contribute to maintain naïve pluripotency in mouse embryonic stem cells |
著者: | Liu, Yajing Yamashita, Jun K. |
著者名の別形: | 山下, 潤 |
キーワード: | Stem cells Naive pluripotency AMPK AICAR p38 Differentiation |
発行日: | 29-Jan-2018 |
出版者: | Elsevier B.V. |
誌名: | Biochemical and Biophysical Research Communications |
巻: | 509 |
号: | 1 |
開始ページ: | 24 |
終了ページ: | 31 |
抄録: | Pluripotent stem cells retain the property to self-renew and differentiate into all cell types under defined conditions. Among mouse embryonic stem cells (ESCs), which are pluripotent but heterogenous in gene expression and morphology, an ESC population cultured in small molecule inhibitors of two kinases, MAPK/ERK kinase (Mek) and Glycogen synthase kinase 3 (Gsk3), and leukemia inhibitory factor (Lif) (2i/L) is considered to be naïve pluripotent with uniform pluripotent machinery operation. Though the gene regulatory mechanism for the naïve pluripotency has been investigated in recent years, it is still not fully elucidated. Here we show a novel signaling involved in the maintenance of naïve pluripotency. An AMP-activated protein kinase (AMPK) activator, AICAR (5-Aminoimidazole-4-carboxamied-1-β-riboside) blocked the differentiation of mouse naïve ESCs in the absence of 2i/L and maintained the naïve state. AICAR with Lif condition induced an almost comparable level of naïve pluripotent gene expression in mouse ESCs. Another AMPK activator, A769662, also showed similar effects. A p38 inhibitor, SB203580, blocked the AMPK activation-elicited naïve state maintenance. On the other hand, p38 activation partially mimicked the maintenance effects of AMPK activators, suggesting that p38 is one of the functional downstream molecules to conduct the AMPK effects. Thus, AMPK pathway should be involved in the molecular circuitry of naïve pluripotency in mouse ESCs. These findings would be a valuable clue to further elucidate the molecular machinery of naïve pluripotency. |
著作権等: | ©2018 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-NDlicense (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
URI: | http://hdl.handle.net/2433/235934 |
DOI(出版社版): | 10.1016/j.bbrc.2018.11.164 |
PubMed ID: | 30573360 |
出現コレクション: | 学術雑誌掲載論文等 |
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