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由Hes1和miR-9的组合调控介导的神经命运决定。

Neural fate decisions mediated by combinatorial regulation of Hes1 and miR-9.

作者信息

Li Shanshan, Liu Yanwei, Liu Zengrong, Wang Ruiqi

机构信息

Institute of Systems Biology, Shanghai University, Shanghai, China.

Department of Mathematics, Shanghai University, Shanghai, China.

出版信息

J Biol Phys. 2016 Jan;42(1):53-68. doi: 10.1007/s10867-015-9391-2. Epub 2015 Jul 9.

Abstract

In the nervous system, Hes1 shows an oscillatory manner in neural progenitors but a persistent one in neurons. Many models involving Hes1 have been provided for the study of neural differentiation but few of them take the role of microRNA into account. It is known that a microRNA, miR-9, plays crucial roles in modulating Hes1 oscillations. However, the roles of miR-9 in controlling Hes1 oscillations and inducing transition between different cell fates still need to be further explored. Here we provide a mathematical model to show the interaction between miR-9 and Hes1, with the aim of understanding how the Hes1 oscillations are produced, how they are controlled, and further, how they are terminated. Based on the experimental findings, the model demonstrates the essential roles of Hes1 and miR-9 in regulating the dynamics of the system. In particular, the model suggests that the balance between miR-9 and Hes1 plays important roles in the choice between progenitor maintenance and neural differentiation. In addition, the synergistic (or antagonistic) effects of several important regulations are investigated so as to elucidate the effects of combinatorial regulation in neural decision-making. Our model provides a qualitative mechanism for understanding the process in neural fate decisions regulated by Hes1 and miR-9.

摘要

在神经系统中,Hes1在神经祖细胞中呈现振荡模式,而在神经元中则持续表达。目前已经提出了许多涉及Hes1的模型来研究神经分化,但其中很少考虑微小RNA的作用。已知一种微小RNA,即miR-9,在调节Hes1振荡中起着关键作用。然而,miR-9在控制Hes1振荡以及诱导不同细胞命运之间转变方面的作用仍有待进一步探索。在此,我们提供一个数学模型来展示miR-9与Hes1之间的相互作用,目的是了解Hes1振荡是如何产生的、如何被控制的,以及进一步了解它们是如何终止的。基于实验结果,该模型证明了Hes1和miR-9在调节系统动态方面的重要作用。特别是,该模型表明miR-9与Hes1之间的平衡在祖细胞维持和神经分化的选择中起着重要作用。此外,研究了几种重要调节的协同(或拮抗)作用,以阐明组合调节在神经决策中的作用。我们的模型为理解由Hes1和miR-9调节的神经命运决定过程提供了一种定性机制。

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