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Title: High Hes1 expression and resultant Ascl1 suppression regulate quiescent vs. active neural stem cells in the adult mouse brain
Authors: Sueda, Risa
Imayoshi, Itaru
Harima, Yukiko
Kageyama, Ryoichiro
Author's alias: 末田, 梨沙
今吉, 格
播磨, 有希子
影山, 龍一郎
Keywords: active neural stem cell
Ascl1
Hes1
notch signaling
oscillatory expression
quiescent neural stem cell
Issue Date: 1-May-2019
Publisher: Cold Spring Harbor Laboratory
Journal title: Genes & Development
Volume: 33
Issue: 9-10
Start page: 511
End page: 523
Abstract: 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.
Description: 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.
Prince Charming's kiss unlocking brain's regenerative potential?. 京都大学プレスリリース. 2019-05-14.
Rights: © 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(Published Version): 10.1101/gad.323196.118
PubMed ID: 30862661
Related Link: http://www.kyoto-u.ac.jp/ja/research/research_results/2018/190313_1.html
https://www.kyoto-u.ac.jp/en/research/research_results/2018/190313_1.html
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