Circadian gene expression in individual fibroblasts: Cell-autonomous and self-sustained oscillators pass time to daughter cells
Circadian gene expression in individual fibroblasts: Cell-autonomous and self-sustained oscillators pass time to daughter cells
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DOI：
10.1016/j.cell.2004.11.015
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发表时间：
2004-11-24
期刊：
影响因子：
64.5
通讯作者：
Schibler, U
中科院分区：
文献类型：
--
作者：
Nagoshi, E;Saini, C;Schibler, U
哺乳动物的昼夜节律系统由位于大脑视交叉上核（SCN）的中央起搏器和大多数外周细胞类型的辅助振荡器组成。虽然已知SCN神经元中的振荡器以自我维持的方式起作用，但外周振荡器被认为在与SCN施加的控制断开时迅速受湿。使用两个报告系统，我们实时监测NIH3T3小鼠成纤维细胞和单个细胞中的昼夜节律基因表达。结合数学建模和细胞共培养实验，这些数据表明，体外培养的成纤维细胞具有自我维持和细胞自主的生物钟，类似于SCN神经元中的生物钟。成纤维细胞的昼夜节律基因表达在细胞分裂过程中持续进行，我们的实验揭示了昼夜节律时钟和细胞分裂时钟之间意想不到的相互作用。具体来说，昼夜节律振荡器使细胞分裂进入定义的时间窗口，有丝分裂引起昼夜节律周期的相移。
The mammalian circadian timing system is composed of a central pacemaker in the suprachiasmatic nucleus (SCN) of the brain and subsidiary oscillators in most peripheral cell types. While oscillators in SCN neurons are known to function in a self-sustained fashion, peripheral oscillators have been thought to damp rapidly when disconnected from the control exerted by the SCN. Using two reporter systems, we monitored circadian gene expression in NIH3T3 mouse fibroblasts in real time and in individual cells. In conjunction with mathematical modeling and cell co-culture experiments, these data demonstrated that in vitro cultured fibroblasts harbor self-sustained and cell-autonomous circadian clocks similar to those operative in SCN neurons. Circadian gene expression in fibroblasts continues during cell division, and our experiments unveiled unexpected interactions between the circadian clock and the cell division clock. Specifically, the circadian oscillator gates cytokinesis to defined time windows, and mitosis elicits phase shifts in circadian cycles.