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<p>Single-cell circadian oscillators exchange extracellular information to sustain coherent circadian rhythms at the tissue level. The circadian clock and the cell cycle couple within cells but the mechanisms underlying this interplay are poorly understood. We show that the loss of extracellular circadian synchronization disrupts circadian and cell cycle coordination within individual cells, impeding collective tissue growth. We use the theory of coupled oscillators combined with live population, and single-cell recordings and precise experimental perturbations. Coherent circadian rhythms yield oscillatory growth patterns, which unveil a global timing regulator of tissue dynamics. Knocking out core circadian elements abolishes the observed effects, highlighting the central role of circadian clock regulation. Our results underscore the role of tissue-level circadian disruption in regulating proliferation, thereby linking disrupted circadian clocks with oncogenic processes. These findings illuminate the intricate interplay between circadian rhythms, cellular signalling and tissue physiology and enhance our understanding of tissue homeostasis and growth regulation in the context of both health and disease.</p>

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Circadian coupling orchestrates cell growth

  • 期刊论文

  • 发表日期：

    2025年3月31日

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  • Nica Gutu,
  • Malthe S. Nordentoft,
  • Marlena Kuhn,
  • Carolin Ector,
  • Marie Möser,
  • Anna-Marie Finger,
  • Mathias Spliid Heltberg,
  • Mogens Høgh Jensen,
  • Ulrich Keilholz,
  • Achim Kramer,
  • Hanspeter Herzel,
  • Adrián E. Granada

摘要

Single-cell circadian oscillators exchange extracellular information to sustain coherent circadian rhythms at the tissue level. The circadian clock and the cell cycle couple within cells but the mechanisms underlying this interplay are poorly understood. We show that the loss of extracellular circadian synchronization disrupts circadian and cell cycle coordination within individual cells, impeding collective tissue growth. We use the theory of coupled oscillators combined with live population, and single-cell recordings and precise experimental perturbations. Coherent circadian rhythms yield oscillatory growth patterns, which unveil a global timing regulator of tissue dynamics. Knocking out core circadian elements abolishes the observed effects, highlighting the central role of circadian clock regulation. Our results underscore the role of tissue-level circadian disruption in regulating proliferation, thereby linking disrupted circadian clocks with oncogenic processes. These findings illuminate the intricate interplay between circadian rhythms, cellular signalling and tissue physiology and enhance our understanding of tissue homeostasis and growth regulation in the context of both health and disease.