德国柏林慈善大学Adrián E. Granada团队揭示了昼夜耦合调控细胞生长。该项研究成果发表在2025年3月31日出版的《自然—物理学》杂志上。

单细胞昼夜节律振荡器交换细胞外信息，以在组织水平维持连贯的昼夜节律。生物钟和细胞周期在细胞内相互作用，但这种相互作用背后的机制知之甚少。研究组发现，细胞外昼夜节律同步的丧失破坏了单个细胞内的昼夜节律和细胞周期协调，阻碍了集体组织的生长。他们使用耦合振子理论，结合活种群、单细胞记录和精确的实验扰动。连贯的昼夜节律产生振荡生长模式，揭示了组织动力学的全球时间调节器。

敲除核心昼夜节律元素会消除观察到的效应，突出昼夜节律钟调节的核心作用。该研究结果强调了组织水平昼夜节律紊乱在调节增殖中的作用，从而将紊乱的昼夜节律钟与致癌过程联系起来。这些发现阐明了昼夜节律、细胞信号传导和组织生理学之间复杂的相互作用，并加深了人们对健康和疾病背景下组织稳态和生长调节的理解。

附：英文原文

Title: Circadian coupling orchestrates cell growth

Author: Gutu, Nica, Nordentoft, Malthe S., Kuhn, Marlena, Ector, Carolin, Mser, Marie, Finger, Anna-Marie, Heltberg, Mathias Spliid, Jensen, Mogens Hgh, Keilholz, Ulrich, Kramer, Achim, Herzel, Hanspeter, Granada, Adrin E.

Issue&Volume: 2025-03-31

Abstract: 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.

DOI: 10.1038/s41567-025-02838-4

Source: https://www.nature.com/articles/s41567-025-02838-4