Circadian Coupling Orchestrates Cell Growth

Author:

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

Abstract

SummarySingle-cell circadian oscillators exchange extracellular information to sustain coherent circadian rhythms at the tissue level. Within cells, the circadian clock and the cell cycle couple, yet the mechanisms governing this interplay remain poorly elucidated. Here, we study the role of extracellular circadian communication in the intracellular coordination between the circadian clock and the cell cycle. We demonstrate that the loss of extracellular circadian synchronization disrupts circadian and cell cycle coordination within individual cells, impeding collective tissue growth. Coherent circadian rhythms yield oscillatory growth patterns, unveiling a global timing regulator of tissue dynamics. Knocking down core circadian elements abolishes observed effects, highlighting the central role of circadian clock regulation. Our research underscores the significance 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 signaling, and tissue physiology, enhancing our understanding of tissue homeostasis and growth regulation in both health and disease contexts.

Publisher

Cold Spring Harbor Laboratory

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