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タイトル: High Hes1 expression and resultant Ascl1 suppression regulate quiescent vs. active neural stem cells in the adult mouse brain
著者: Sueda, Risa
Imayoshi, Itaru
Harima, Yukiko
Kageyama, Ryoichiro
著者名の別形: 末田, 梨沙
今吉, 格
播磨, 有希子
影山, 龍一郎
キーワード: active neural stem cell
Ascl1
Hes1
notch signaling
oscillatory expression
quiescent neural stem cell
発行日: 2019
出版者: Cold Spring Harbor Laboratory
誌名: Genes & Development
巻: 33
抄録: Somatic stem/progenitor cells are active in embryonic tissues but quiescent in many adult tissues. The detailed mechanisms that regulate active versus quiescent stem cell states are largely unknown. In active neural stem cells, Hes1 expression oscillates and drives cyclic expression of the proneural gene Ascl1, which activates cell proliferation. Here, we found that in quiescent neural stem cells in the adult mouse brain, Hes1 levels are oscillatory, although the peaks and troughs are higher than those in active neural stem cells, causing Ascl1 expression to be continuously suppressed. Inactivation of Hes1 and its related genes up-regulates Ascl1 expression and increases neurogenesis. This causes rapid depletion of neural stem cells and premature termination of neurogenesis. Conversely, sustained Hes1 expression represses Ascl1, inhibits neurogenesis, and maintains quiescent neural stem cells. In contrast, induction of Ascl1 oscillations activates neural stem cells and increases neurogenesis in the adult mouse brain. Thus, Ascl1 oscillations, which normally depend on Hes1 oscillations, regulate the active state, while high Hes1 expression and resultant Ascl1 suppression promote quiescence in neural stem cells.
記述: 神経幹細胞の休眠化・活性化機構を解明 --眠った神経幹細胞から神経細胞をつくりだす--. 京都大学プレスリリース. 2019-03-14.
著作権等: © 2019 Sueda et al.; Published by Cold Spring Harbor Laboratory Press. This article, published in Genes & Development, is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
URI: http://hdl.handle.net/2433/237316
DOI(出版社版): 10.1101/gad.323196.118
関連リンク: http://www.kyoto-u.ac.jp/ja/research/research_results/2018/190313_1.html
出現コレクション:学術雑誌掲載論文等

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