瞬时creb介导的转录是直接神经元重编程的关键。

Neurogenesis (Austin, Tex.) Pub Date : 2017-02-06 eCollection Date: 2017-01-01 DOI:10.1080/23262133.2017.1285383
Sergio Gascón, Felipe Ortega, Magdalena Götz
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引用次数: 15

摘要

神经元决定因子和/或小分子(如Forskolin (Fk))的组合可用于将不同类型的细胞转化为神经元。由于已知Fk可以激活camp依赖性通路,包括CREB活性,我们在此旨在确定CREB在重编程中的作用,包括其时间分布。我们发现,瞬时表达显性阳性的CREB-VP16,随后由显性阴性的ICER介导其失活,可改善由神经源性决定因子Ascl1介导的星形胶质细胞的神经元转化。相反,CREB-VP16的持续过度激活或ICER的持续抑制会干扰神经元重编程,后者会增强细胞死亡。综上所述,我们的工作表明瞬时CREB激活是神经元重编程的关键效应。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Transient CREB-mediated transcription is key in direct neuronal reprogramming.

Transient CREB-mediated transcription is key in direct neuronal reprogramming.

Transient CREB-mediated transcription is key in direct neuronal reprogramming.

Transient CREB-mediated transcription is key in direct neuronal reprogramming.

Combinations of neuronal determinants and/or small-molecules such as Forskolin (Fk) can be used to convert different cell types into neurons. As Fk is known to activate cAMP-dependent pathways including CREB-activity, we aimed here to determine the role of CREB in reprogramming - including its temporal profile. We show that transient expression of the dominant-positive CREB-VP16 followed by its inactivation mediated by the dominant-negative ICER improves neuronal conversion of astrocytes mediated by the neurogenic determinant Ascl1. Contrarily, persistent over-activation by CREB-VP16 or persistent inhibition by ICER interferes with neuronal reprogramming, with the latter enhancing cell death. Taken together our work shows transient CREB activation as a key effector in neuronal reprogramming.

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