microRNA input into a neural ultradian oscillator controls emergence and timing of alternative cell states.
microRNA input into a neural ultradian oscillator controls emergence and timing of alternative cell states.
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DOI：
10.1038/ncomms4399
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发表时间：
2014-03-04
影响因子：
16.6
通讯作者：
Papalopulu, Nancy
中科院分区：
文献类型：
--
作者：
Goodfellow, Marc;Phillips, Nicholas E.;Manning, Cerys;Galla, Tobias;Papalopulu, Nancy
祖细胞维持、定时分化和进入静止状态的可能性是任何器官系统发育的三个基本过程。在神经系统中，前体细胞在转录抑制因子Hes1的表达上表现出短暂的振荡，而神经元和静止的前体细胞分别显示稳定的低水平和高水平的Hes1表达。在这里，我们使用实验数据来建立Hes1和microRNA miR-9之间的双负相互作用的数学模型，目的是了解细胞如何从一种状态转换到另一种状态。结果表明，miR-9的输入可以调节Hes1振荡器的振荡动力学，使系统具有双稳特性和测量微分时间的能力。我们的结果表明，一个相对简单和广泛的交叉抑制相互作用网络为祖细胞的维持、分化的时机和替代细胞状态的出现提供了一个统一的框架。HES1是祖细胞维持和定时分化的重要调节因子，表现为振荡表达。在这里，作者结合实验数据和数学模型表明，miRNA-9和Hes1之间的相互作用可以预测祖细胞从一种细胞状态到另一种细胞状态的转变，以及这种转变的时间。
Progenitor maintenance, timed differentiation and the potential to enter quiescence are three fundamental processes that underlie the development of any organ system. In the nervous system, progenitor cells show short-period oscillations in the expression of the transcriptional repressor Hes1, while neurons and quiescent progenitors show stable low and high levels of Hes1, respectively. Here we use experimental data to develop a mathematical model of the double-negative interaction between Hes1 and a microRNA, miR-9, with the aim of understanding how cells transition from one state to another. We show that the input of miR-9 into the Hes1 oscillator tunes its oscillatory dynamics, and endows the system with bistability and the ability to measure time to differentiation. Our results suggest that a relatively simple and widespread network of cross-repressive interactions provides a unifying framework for progenitor maintenance, the timing of differentiation and the emergence of alternative cell states. Hes1 is an important regulator of progenitor maintenance and timed differentiation, which shows oscillatory expression. Here, the authors combine experimental data and mathematical modelling to show that the interaction between miRNA-9 and Hes1 can predict progenitor transition from one cell state to another, as well as the timing of this transition.
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影响因子：
16.2
作者：
Franco SJ;Müller U
通讯作者：
Müller U
影响因子：
56.9
作者：
Hirata, H;Yoshiura, S;Kageyama, R
通讯作者：
Kageyama, R
影响因子：
4.6
作者：
Kageyama, Ryoichiro;Ohtsuka, Toshiyuki;Kobayashi, Taeko
通讯作者：
Kobayashi, Taeko
DOI：
10.1038/nrm3591
发表时间：
2013-06
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.6
作者：
Hatakeyama, J;Bessho, Y;Kageyama, R
通讯作者：
Kageyama, R