Determination of cell fate selection during phage lambda infection
Determination of cell fate selection during phage lambda infection
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DOI：
10.1073/pnas.0808831105
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发表时间：
2008-12-30
影响因子：
11.1
通讯作者：
Endy, Drew
中科院分区：
文献类型：
--
作者：
St-Pierre, Francois;Endy, Drew
大肠杆菌的λ噬菌体感染可导致不同的细胞命运结果。例如，一些细胞溶解，而另一些细胞作为溶原细胞存活。λ感染的定量生物物理模型支持这一假设，即λ感染过程中个体分子事件的时间自发差异导致细胞命运选择的变化。从这个分析的基础上，λ裂解-溶原性决定现在作为一个范例，内在的分子噪音如何影响细胞行为，驱动发育过程，并产生人口异质性。在这里，我们报告的实验证据，值得重新考虑这个框架。通过使用细胞分级，平板，和单细胞荧光显微镜，我们发现，感染前存在的细胞之间的物理差异偏差λ发育结果。具体而言，感染时细胞体积的变化可用于帮助预测细胞命运：细胞体积增加约2倍导致溶原性概率降低4至5倍。现在认为是随机的其他细胞命运决定也可能由预先存在的变异决定。
Bacteriophage lambda infection of Escherichia coli can result in distinct cell fate outcomes. For example, some cells lyse whereas others survive as lysogens. A quantitative biophysical model of lambda infection supports the hypothesis that spontaneous differences in the timing of individual molecular events during lambda infection leads to variation in the selection of cell fates. Building from this analysis, the lambda lysis-lysogeny decision now serves as a paradigm for how intrinsic molecular noise can influence cellular behavior, drive developmental processes, and produce population heterogeneity. Here, we report experimental evidence that warrants reconsidering this framework. By using cell fractioning, plating, and single-cell fluorescent microscopy, we find that physical differences among cells present before infection bias lambda developmental outcomes. Specifically, variation in cell volume at the time of infection can be used to help predict cell fate: a approximate to 2-fold increase in cell volume results in a 4- to 5-fold decrease in the probability of lysogeny. Other cell fate decisions now thought to be stochastic might also be determined by pre-existing variation.