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Circa-SCOPE: high-throughput live single-cell imaging method for analysis of circadian clock resetting

Author

Listed:
  • Gal Manella

    (Weizmann Institute of Science)

  • Dan Aizik

    (Weizmann Institute of Science)

  • Rona Aviram

    (Weizmann Institute of Science)

  • Marina Golik

    (Weizmann Institute of Science)

  • Gad Asher

    (Weizmann Institute of Science)

Abstract

Circadian clocks are self-sustained and cell-autonomous oscillators. They respond to various extracellular cues depending on the time-of-day and the signal intensity. Phase Transition Curves (PTCs) are instrumental in uncovering the full repertoire of responses to a given signal. However, the current methodologies for reconstructing PTCs are low-throughput, laborious, and resource- and time-consuming. We report here the development of an efficient and high throughput assay, dubbed Circadian Single-Cell Oscillators PTC Extraction (Circa-SCOPE) for generating high-resolution PTCs. This methodology relies on continuous monitoring of single-cell oscillations to reconstruct a full PTC from a single culture, upon a one-time intervention. Using Circa-SCOPE, we characterize the effects of various pharmacological and blood-borne resetting cues, at high temporal resolution and a wide concentration range. Thus, Circa-SCOPE is a powerful tool for comprehensive analysis and screening for circadian clocks’ resetting cues, and can be valuable for basic as well as translational research.

Suggested Citation

  • Gal Manella & Dan Aizik & Rona Aviram & Marina Golik & Gad Asher, 2021. "Circa-SCOPE: high-throughput live single-cell imaging method for analysis of circadian clock resetting," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26210-1
    DOI: 10.1038/s41467-021-26210-1
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    References listed on IDEAS

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    1. Satoshi Koinuma & Hiroshi Kori & Isao T Tokuda & Kazuhiro Yagita & Yasufumi Shigeyoshi, 2017. "Transition of phase response properties and singularity in the circadian limit cycle of cultured cells," PLOS ONE, Public Library of Science, vol. 12(7), pages 1-16, July.
    2. Berens, Philipp, 2009. "CircStat: A MATLAB Toolbox for Circular Statistics," Journal of Statistical Software, Foundation for Open Access Statistics, vol. 31(i10).
    3. Kosaku Masuda & Isao T. Tokuda & Norihito Nakamichi & Hirokazu Fukuda, 2021. "The singularity response reveals entrainment properties of the plant circadian clock," Nature Communications, Nature, vol. 12(1), pages 1-7, December.
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    1. Kosaku Masuda & Naohiro Kon & Kosuke Iizuka & Yoshitaka Fukada & Takeshi Sakurai & Arisa Hirano, 2023. "Singularity response reveals entrainment properties in mammalian circadian clock," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    2. Makoto Takeo & Koh-ei Toyoshima & Riho Fujimoto & Tomoyo Iga & Miki Takase & Miho Ogawa & Takashi Tsuji, 2023. "Cyclical dermal micro-niche switching governs the morphological infradian rhythm of mouse zigzag hair," Nature Communications, Nature, vol. 14(1), pages 1-13, December.

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