Isomura Akihiro, Ogushi Fumiko, Kori Hiroshi, Kageyama Ryoichiro
Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.
Japan Science and Technology Agency, PRESTO (Precursory Research for Embryonic Science and Technology), Saitama 332-0012, Japan.
Genes Dev. 2017 Mar 1;31(5):524-535. doi: 10.1101/gad.294546.116. Epub 2017 Apr 3.
Cells communicate with each other to coordinate their gene activities at the population level through signaling pathways. It has been shown that many gene activities are oscillatory and that the frequency and phase of oscillatory gene expression encode various types of information. However, whether or how such oscillatory information is transmitted from cell to cell remains unknown. Here, we developed an integrated approach that combines optogenetic perturbations and single-cell bioluminescence imaging to visualize and reconstitute synchronized oscillatory gene expression in signal-sending and signal-receiving processes. We found that intracellular and intercellular periodic inputs of Notch signaling entrain intrinsic oscillations by frequency tuning and phase shifting at the single-cell level. In this way, the oscillation dynamics are transmitted through Notch signaling, thereby synchronizing the population of oscillators. Thus, this approach enabled us to control and monitor dynamic cell-to-cell transfer of oscillatory information to coordinate gene expression patterns at the population level.
细胞通过信号通路相互通讯，以在群体水平上协调它们的基因活动。研究表明，许多基因活动是振荡性的，并且振荡基因表达的频率和相位编码了各种类型的信息。然而，这种振荡信息是否以及如何在细胞间传递仍然未知。在这里，我们开发了一种综合方法，该方法结合了光遗传学扰动和单细胞生物发光成像，以可视化和重建信号发送和信号接收过程中同步的振荡基因表达。我们发现，Notch信号的细胞内和细胞间周期性输入通过单细胞水平的频率调谐和相移来夹带内在振荡。通过这种方式，振荡动力学通过Notch信号传递，从而使振荡器群体同步。因此，这种方法使我们能够控制和监测振荡信息在细胞间的动态传递，以在群体水平上协调基因表达模式。
