TAZ Represses the Neuronal Commitment of Neural Stem Cells.
TAZ Represses the Neuronal Commitment of Neural Stem Cells.
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TAZ抑制神经干细胞的神经元承诺。
DOI：
10.3390/cells9102230
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发表时间：
2020-10-02
期刊：
影响因子：
6
通讯作者：
Cuadrado A
中科院分区：
文献类型：
--
作者：
Robledinos-Antón N;Escoll M;Guan KL;Cuadrado A
哺乳动物大脑神经干祖细胞（NSPCs）的静止、增殖和重编程调控机制仍不明确。在这里，我们研究了由WNT和Hippo通路调控的转录辅助因子TAZ在NSPCs体内平衡中的作用。我们发现，在纹状体脑室下区和齿状回颗粒区等小鼠神经源性壁龛中，TAZ在NSPCs中高度表达，并随着年龄的增长而下降。此外，TAZ在两个神经发生区域的未成熟神经元中表达缺失。为了从机制上表征TAZ在神经元分化中的作用，我们使用中脑来源的NSPC细胞系ReNcell VM在非动物模型中复制影响NSPC分化的因素到神经元谱系。NSPCs中TAZ的敲除和强迫表达分别导致神经元分化增加和减少。teads敲低表明这些TAZ合作伙伴是抑制NSPCs对神经元分化的承诺所必需的。TAZ/TEAD系统的遗传操作表明其参与SOX2和前神经元基因ASCL1、NEUROG2和NEUROD1的转录抑制，导致神经发生障碍。TAZ通常被认为是促进干细胞增殖的转录共激活因子，但我们的研究表明，TAZ还具有抑制神经元分化的功能。
The mechanisms involved in regulation of quiescence, proliferation, and reprogramming of Neural Stem Progenitor Cells (NSPCs) of the mammalian brain are still poorly defined. Here, we studied the role of the transcriptional co-factor TAZ, regulated by the WNT and Hippo pathways, in the homeostasis of NSPCs. We found that, in the murine neurogenic niches of the striatal subventricular zone and the dentate gyrus granular zone, TAZ is highly expressed in NSPCs and declines with ageing. Moreover, TAZ expression is lost in immature neurons of both neurogenic regions. To characterize mechanistically the role of TAZ in neuronal differentiation, we used the midbrain-derived NSPC line ReNcell VM to replicate in a non-animal model the factors influencing NSPC differentiation to the neuronal lineage. TAZ knock-down and forced expression in NSPCs led to increased and reduced neuronal differentiation, respectively. TEADs-knockdown indicated that these TAZ co-partners are required for the suppression of NSPCs commitment to neuronal differentiation. Genetic manipulation of the TAZ/TEAD system showed its participation in transcriptional repression of SOX2 and the proneuronal genes ASCL1, NEUROG2, and NEUROD1, leading to impediment of neurogenesis. TAZ is usually considered a transcriptional co-activator promoting stem cell proliferation, but our study indicates an additional function as a repressor of neuronal differentiation.
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影响因子：
23.9
作者：
Encinas, Juan M.;Michurina, Tatyana V.;Peunova, Natalia;Park, June-Hee;Tordo, Julie;Peterson, Daniel A.;Fishell, Gord;Koulakov, Alex;Enikolopov, Grigori
通讯作者：
Enikolopov, Grigori
影响因子：
56.9
作者：
Hong, JH;Hwang, ES;Yaffe, MB
通讯作者：
Yaffe, MB
影响因子：
64.5
作者：
Azzolin, Luca;Panciera, Tito;Piccolo, Stefano
通讯作者：
Piccolo, Stefano
影响因子：
64.5
作者：
Azzolin, Luca;Zanconato, Francesca;Piccolo, Stefano
通讯作者：
Piccolo, Stefano
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影响因子：
16
作者：
Galli GG;Carrara M;Yuan WC;Valdes-Quezada C;Gurung B;Pepe-Mooney B;Zhang T;Geeven G;Gray NS;de Laat W;Calogero RA;Camargo FD
通讯作者：
Camargo FD