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Temporal integration of mitogen history in mother cells controls proliferation of daughter cells
Science ( IF 56.9 ) Pub Date : 2020-04-02 , DOI: 10.1126/science.aay8241
Mingwei Min 1 , Yao Rong 1, 2 , Chengzhe Tian 1 , Sabrina L Spencer 1
Affiliation  

How cells monitor mitogen availability Classical experiments indicated that cells sense the mitogens or growth factors that control cell division within a limited window during the cell cycle. Min et al. reexamined this issue with high-throughput live-cell imaging and temporally controlled perturbations to more closely monitor dynamic signal processing. Human epithelial cells in culture integrated the mitogenic signals sensed throughout the cell cycle. One important factor was the control of translation rates, which influenced the amount of cyclin D, thus regulating proliferation. The results may also help to explain how cells maintain a uniform size. Science, this issue p. 1261 Human epithelial cells can monitor mitogen availability throughout the cell cycle to regulate cell division. Multicellular organisms use mitogens to regulate cell proliferation, but how fluctuating mitogenic signals are converted into proliferation-quiescence decisions is poorly understood. In this work, we combined live-cell imaging with temporally controlled perturbations to determine the time scale and mechanisms underlying this system in human cells. Contrary to the textbook model that cells sense mitogen availability only in the G1 cell cycle phase, we find that mitogenic signaling is temporally integrated throughout the entire mother cell cycle and that even a 1-hour lapse in mitogen signaling can influence cell proliferation more than 12 hours later. Protein translation rates serve as the integrator that proportionally converts mitogen history into corresponding levels of cyclin D in the G2 phase of the mother cell, which controls the proliferation-quiescence decision in daughter cells and thereby couples protein production with cell proliferation.

中文翻译:

母细胞中丝裂原历史的时间整合控制子细胞的增殖

细胞如何监测有丝分裂原的可用性 经典实验表明,细胞感知有丝分裂原或生长因子,它们在细胞周期的有限窗口内控制细胞分裂。敏等人。通过高通量活细胞成像和时间控制扰动重新审视了这个问题,以更密切地监测动态信号处理。培养中的人类上皮细胞整合了在整个细胞周期中感知到的促有丝分裂信号。一个重要因素是翻译率的控制,它影响细胞周期蛋白 D 的数量,从而调节增殖。结果也可能有助于解释细胞如何保持统一的大小。科学,这个问题 p。1261 人类上皮细胞可以在整个细胞周期中监测有丝分裂原的可用性,以调节细胞分裂。多细胞生物使用有丝分裂原来调节细胞增殖,但人们对波动的有丝分裂信号如何转化为增殖-静止决定知之甚少。在这项工作中,我们将活细胞成像与时间控制的扰动相结合,以确定人体细胞中该系统的时间尺度和机制。与细胞仅在 G1 细胞周期阶段感知有丝分裂素可用性的教科书模型相反,我们发现有丝分裂信号在整个母细胞周期中暂时整合,即使有 1 小时的有丝分裂信号中断也会影响细胞增殖超过 12几小时后。蛋白质翻译率作为积分器,将有丝分裂原的历史按比例转化为母细胞 G2 期相应水平的细胞周期蛋白 D,
更新日期:2020-04-02
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