Cell cycle arrest determines adult neural stem cell ontogeny by an embryonic Notch-nonoscillatory Hey1 module.
Cell cycle arrest determines adult neural stem cell ontogeny by an embryonic Notch-nonoscillatory Hey1 module.
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DOI：
10.1038/s41467-021-26605-0
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发表时间：
2021-11-12
影响因子：
16.6
通讯作者：
Gotoh Y
中科院分区：
文献类型：
--
作者：
Harada Y;Yamada M;Imayoshi I;Kageyama R;Suzuki Y;Kuniya T;Furutachi S;Kawaguchi D;Gotoh Y
成年小鼠大脑中的静止神经干细胞（NSCs）是调节先天和适应性行为的神经发生的来源。脑室下区的成人NSCs来源于胚胎神经干细胞-祖细胞（NPCs）的一个亚群，其特征是相对于构建大脑的更丰富的快速循环NPCs而言，细胞周期较慢。然而，如何缓慢的细胞周期可以导致成人NSCs的建立在很大程度上仍然是未知的。在这里，我们证明Notch和效应器Hey1形成了一个模块，该模块在缓慢分裂的npc中被细胞周期阻滞上调。与Notch效应因子Hes1和Hes5在快速循环祖细胞中的振荡表达不同，Hey1表现出非振荡的稳态表达模式，有助于NSCs的长期维持。这些发现揭示了Notch效应物的一种新的分工，其中细胞周期率会影响效应物的选择和细胞命运。成体神经干细胞来源于一个缓慢循环祖细胞的胚胎群体，尽管如何降低循环速度导致成年群体的建立仍然是难以捉摸的。在这里，他们表明由慢循环诱导的非振荡Notch-Hey信号有助于神经干细胞的长期维持。
Quiescent neural stem cells (NSCs) in the adult mouse brain are the source of neurogenesis that regulates innate and adaptive behaviors. Adult NSCs in the subventricular zone are derived from a subpopulation of embryonic neural stem-progenitor cells (NPCs) that is characterized by a slower cell cycle relative to the more abundant rapid cycling NPCs that build the brain. Yet, how slow cell cycle can cause the establishment of adult NSCs remains largely unknown. Here, we demonstrate that Notch and an effector Hey1 form a module that is upregulated by cell cycle arrest in slowly dividing NPCs. In contrast to the oscillatory expression of the Notch effectors Hes1 and Hes5 in fast cycling progenitors, Hey1 displays a non-oscillatory stationary expression pattern and contributes to the long-term maintenance of NSCs. These findings reveal a novel division of labor in Notch effectors where cell cycle rate biases effector selection and cell fate. Adult neural stem cells are derived from an embryonic population of slowcycling progenitor cells, though how reduced cycling speed leads to establishment of the adult population has remained elusive. Here they show that non-oscillatory Notch-Hey signaling induced by slow-cycling contributes to long term maintenance of neural stem cells.
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影响因子：
16.6
作者：
Goodfellow, Marc;Phillips, Nicholas E.;Manning, Cerys;Galla, Tobias;Papalopulu, Nancy
通讯作者：
Papalopulu, Nancy
影响因子：
56.9
作者：
Cheng, T;Rodrigues, N;Scadden, DT
通讯作者：
Scadden, DT
影响因子：
4.6
作者：
Bansod, Shama;Kageyama, Ryoichiro;Ohtsuka, Toshiyuki
通讯作者：
Ohtsuka, Toshiyuki
影响因子：
46.9
作者：
Foudi, Adlen;Hochedlinger, Konrad;Van Buren, Denille;Schindler, Jeffrey W.;Jaenisch, Rudolf;Carey, Vincent;Hock, Hanno
通讯作者：
Hock, Hanno
影响因子：
4.6
作者：
Hatakeyama, J;Bessho, Y;Kageyama, R
通讯作者：
Kageyama, R