Akihiro Isomura^1,2, Fumiko Ogushi³, Hiroshi Kori³, Ryoichiro Kageyama^2,4,5,6

¹ Japan Science and Technology Agency, PRESTO (Precursory Research for Embryonic Science and Technology), ² Institute for Frontier Life and Medical Sciences, Kyoto University,³ Department of Information Sciences, Ochanomizu University, ⁴ Institute for Integrated Cell-Material Sciences (World Premier International research Center [WPI]-iCeMS), Kyoto University、⁵ Graduate School of Biostudies, Kyoto University, ⁶ Graduate School of Medicine, Kyoto University

“Optogenetic perturbation and bioluminescence imaging to analyze cell-to-cell transfer of oscillatory information”

Genes & Development 31, 524–535 (2017). DOI: 10.1101/gad.294546.116

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.

Figure：Optogenetic regulation of Dll1 expression in sender cells and oscillatory responses in receiver cells.

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