Singularity response reveals entrainment properties in mammalian circadian clock

Kosaku Masuda, Naohiro Kon, Kosuke Iizuka, Yoshitaka Fukada, Takeshi Sakurai () and Arisa Hirano ()
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Kosaku Masuda: University of Tsukuba
Naohiro Kon: Nagoya University
Kosuke Iizuka: Nagoya University
Yoshitaka Fukada: Graduate School of Science, The University of Tokyo
Takeshi Sakurai: University of Tsukuba
Arisa Hirano: University of Tsukuba

Nature Communications, 2023, vol. 14, issue 1, 1-11

Abstract: Abstract Entrainment is characterized by phase response curves (PRCs), which provide a summary of responses to perturbations at each circadian phase. The synchronization of mammalian circadian clocks is accomplished through the receipt of a variety of inputs from both internal and external time cues. A comprehensive comparison of PRCs for various stimuli in each tissue is required. Herein, we demonstrate that PRCs in mammalian cells can be characterized using a recently developed estimation method based on singularity response (SR), which represents the response of desynchronized cellular clocks. We confirmed that PRCs can be reconstructed using single SR measurements and quantified response properties for various stimuli in several cell lines. SR analysis reveals that the phase and amplitude after resetting are distinguishable among stimuli. SRs in tissue slice cultures reveal tissue-specific entrainment properties. These results demonstrate that SRs can be employed to unveil entrainment mechanisms with diverse stimuli in multiscale mammalian clocks.

Date: 2023
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DOI: 10.1038/s41467-023-38392-x

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