A noisy linear map underlies oscillations in cell size and gene expression in bacteria.
A noisy linear map underlies oscillations in cell size and gene expression in bacteria.
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DOI：
10.1038/nature14562
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发表时间：
2015-07-16
期刊：
影响因子：
64.8
通讯作者：
You L
中科院分区：
文献类型：
--
作者：
Tanouchi Y;Pai A;Park H;Huang S;Stamatov R;Buchler NE;You L
在细菌生长过程中，一个细胞在分裂前大小大约增加一倍，然后分裂成两个子细胞。这一过程受到细胞噪声的固有扰动，因此需要调节细胞大小的稳态。由于难以长时间以高通量的方式确定单个细菌的大小，因此细胞大小控制的机制及其动力学后果仍然知之甚少。在这里，我们测量和分析了不同大肠杆菌菌株和生长条件下的长期单细胞生长和分裂。我们发现群体中的一部分细胞在细胞大小上表现出短暂的振荡，其周期跨越多代（bbb10）。我们的分析揭示了一个控制细胞大小的简单规律——一个有噪声的线性图——解释了所有菌株中这些细胞大小振荡的起源。这个有噪声的线性映射实现了对细胞大小控制的负反馈：初始大小较大的细胞倾向于更早分裂，而初始大小较小的细胞倾向于更晚分裂。将细胞生长和分裂的模拟与实验数据相结合，我们证明了这种嘈杂的线性图谱不仅在细胞大小上产生瞬态振荡，而且在构成基因表达上也产生瞬态振荡。我们的工作为细菌细胞大小调节的动力学提供了新的见解，并对所涉及的生理过程产生了影响。
During bacterial growth, a cell approximately doubles in size prior to division, upon which it splits into two daughter cells. This process is subjected to the inherent perturbations of cellular noise and thus requires regulation for cell-size homeostasis. The mechanisms underlying cell-size control and their dynamics consequences remain poorly understood due to the difficulty in sizing individual bacteria over long periods of time in a high-throughput manner. Here, we measured and analyzed long-term, single-cell growth and division across different Escherichia coli strains and growth conditions. We found that a subset of cells in a population exhibited transient oscillations in cell size with periods that stretch across multiple (>10) generations. Our analysis revealed that a simple law governing cell size control – a noisy linear map – explains the origins of these cell-size oscillations across all strains. This noisy linear map implements a negative feedback on cell-size control: a cell with a larger initial size tends to divide earlier, whereas one with a smaller initial size tends to divide later. Combining simulations of cell growth and division with experimental data, we demonstrate that this noisy linear map generates transient oscillations, not just in cell size, but also in constitutive gene expression. Our work provides new insights into the dynamics of bacterial cell-size regulation with implications for the physiological processes involved.