Transition of phase response properties and singularity in the circadian limit cycle of cultured cells.
Transition of phase response properties and singularity in the circadian limit cycle of cultured cells.
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DOI：
10.1371/journal.pone.0181223
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Shigeyoshi Y
中科院分区：
文献类型：
--
作者：
Koinuma S;Kori H;Tokuda IT;Yagita K;Shigeyoshi Y
生物钟系统被认为是生物钟基因和蛋白质相互作用的极限环振荡器。在这里，我们研究了哺乳动物的昼夜节律振荡几何之前和之后的扰动。我们检测到的奇点和过渡从1型到0型相位响应曲线（PRC），并确定嵌入维数，以显示需要多少变量来描述的极限环振荡和松弛过程后的扰动。作为干扰，将毛喉素（FK）给予表达Per 2：：luc基因的Rat-1细胞。通过广泛而精细地改变扰动的相位和强度，我们检测到PRC从1型到0型的转变以及可能的奇异转变点，其性质与我们对噪声Goodwin模型的数值模拟非常一致，Goodwin模型是核心时钟基因转录-翻译反馈回路的简单而规范的模型。此外，我们估计了扰动前后极限环的嵌入维数。极限环的轨迹是二维的，但随着状态点的扰动移出轨迹，松弛过程一般嵌入更高的维度。随着FK剂量的增加，每个剂量的平均嵌入维数增加，但大部分弛豫过程通常嵌入在四维中。这些研究结果支持在哺乳动物细胞中存在昼夜节律极限环振荡器，并表明，少数变量确定扰动后的松弛过程。
The circadian system has been regarded as a limit cycle oscillator constructed by the integrated interaction of clock genes and proteins. Here, we investigated a mammalian circadian oscillation geometrically before and after a perturbation. We detected the singular point and transition from a type 1 to type 0 phase response curve (PRC) and determined the embedding dimension to show how many variables are needed to describe the limit cycle oscillation and relaxation process after a perturbation. As a perturbation, forskolin (FK) was administered to Rat-1 cells expressing the Per2::luc gene. By broadly and finely changing the phase and strength of the perturbation, we detected the transition of the PRC from type 1 to type 0 and a possible singular transition point, the property of which agreed quite well with our numerical simulation of the noisy Goodwin model, a simple yet canonical model for the transcription-translation feedback loop of the core clock genes. Furthermore, we estimated the embedding dimension of the limit cycle before and after the perturbation. The trajectory of the limit cycle was embedded in two dimensions but with the perturbation of the state point moved out of the trajectory, the relaxation process was generally embedded in higher dimensions. The average number of embedding dimensions at each dose of FK increased as the FK dose increased but most of the relaxation process was generally embedded within four dimensions. These findings support the existence of a circadian limit cycle oscillator in mammalian cells and suggest that a small number of variables determine the relaxation process after a perturbation.