Sainsbury Laboratory, University of Cambridge, CB2 1LR Cambridge, United Kingdom.
Department of Mathematics, Imperial College London, SW7 2AZ London, United Kingdom
Proc Natl Acad Sci U S A. 2018 Nov 27;115(48):E11415-E11424. doi: 10.1073/pnas.1811309115. Epub 2018 Nov 8.
How cells maintain their size has been extensively studied under constant conditions. In the wild, however, cells rarely experience constant environments. Here, we examine how the 24-h circadian clock and environmental cycles modulate cell size control and division timings in the cyanobacterium using single-cell time-lapse microscopy. Under constant light, wild-type cells follow an apparent sizer-like principle. Closer inspection reveals that the clock generates two subpopulations, with cells born in the subjective day following different division rules from cells born in subjective night. A stochastic model explains how this behavior emerges from the interaction of cell size control with the clock. We demonstrate that the clock continuously modulates the probability of cell division throughout day and night, rather than solely applying an on-off gate to division, as previously proposed. Iterating between modeling and experiments, we go on to identify an effective coupling of the division rate to time of day through the combined effects of the environment and the clock on cell division. Under naturally graded light-dark cycles, this coupling narrows the time window of cell divisions and shifts divisions away from when light levels are low and cell growth is reduced. Our analysis allows us to disentangle, and predict the effects of, the complex interactions between the environment, clock, and cell size control.
细胞如何维持其大小在恒定条件下已经得到了广泛的研究。然而，在自然界中，细胞很少经历恒定的环境。在这里，我们使用单细胞延时显微镜检查 24 小时昼夜节律和环境周期如何调节蓝藻中的细胞大小控制和分裂时间。在恒定的光线下，野生型细胞遵循明显的类似大小的原则。更仔细的观察表明，时钟产生两个亚群，在主观白天出生的细胞与在主观夜晚出生的细胞遵循不同的分裂规则。随机模型解释了这种行为如何从细胞大小控制与时钟的相互作用中产生。我们证明，时钟在白天和黑夜不断地调节细胞分裂的概率，而不是像以前提出的那样仅仅对分裂施加开/关门。通过建模和实验的反复迭代，我们继续确定通过环境和时钟对细胞分裂的综合影响，将分裂率与一天中的时间有效地耦合起来。在自然分级的明暗循环下，这种耦合缩小了细胞分裂的时间窗口，并将分裂转移到光水平较低和细胞生长减少的时候。我们的分析使我们能够区分环境、时钟和细胞大小控制之间复杂相互作用的影响，并对其进行预测。
