Cells often respond to environmental stimuli by activating specific transcription factors. Upon exposure to glucose limitation stress, it is known that yeast Saccharomyces cerevisiae cells dephosphorylate the general stress response factor Msn2, leading to its nuclear localization, which in turn activates the expression of many genes. However, the precise dynamics of Msn2 nucleocytoplasmic translocations and whether they are inherited over multiple generations in a stress-dependent manner are not well understood. Tracking Msn2 localization events in yeast lineages grown on a microfluidic chip, here we report how cells modulate the amplitude, duration, frequency, and dynamic pattern of the localization events in response to glucose limitation stress. Single yeast cells were found to modulate the amplitude and frequency of Msn2 nuclear localization, but not its duration. Moreover, the Msn2 localization frequency was epigenetically inherited in descendants of mother cells, leading to a decrease in cell-to-cell variation in localization frequency. An analysis of the time dynamic patterns of nuclear localizations between genealogically related cell pairs using an information theory approach found that the magnitude of pattern similarity increased with stress intensity and was strongly inherited by the descendant cells at the highest stress level. By dissecting how general stress response dynamics is contributed by different modulation schemes over long time scales, our work provides insight into which scheme evolution might have acted on to optimize fitness in stressful environments.

中文翻译：

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单细胞家谱揭示的遗传应激反应动力学。

细胞通常通过激活特定的转录因子来响应环境刺激。已知在暴露于葡萄糖限制应激时，酵母酿酒酵母（Saccharomyces cerevisiae）细胞使总的应激反应因子Msn2去磷酸化，导致其核定位，进而激活许多基因的表达。但是，Msn2核质易位的确切动态，以及它们是否以压力依赖的方式在多个世代中被继承还不是很清楚。跟踪微流控芯片上生长的酵母谱系中的Msn2定位事件，在这里我们报告细胞如何响应葡萄糖限制应激来调节定位事件的幅度，持续时间，频率和动态模式。发现单个酵母细胞可以调节Msn2核定位的幅度和频率，但不能调节其持续时间。此外，Msn2的定位频率是在后代中在母细胞的后代中遗传的，导致定位频率的单元间变化减少。使用信息论方法分析家系相关细胞对之间的核定位的时间动态模式，发现模式相似性的大小随压力强度而增加，并在最高压力水平下被后代细胞强烈遗传。通过剖析长期范围内不同调制方案对一般压力响应动力学的贡献，我们的工作提供了对哪些方案可能在优化压力环境中的适应性方面发挥作用的见解。使用信息论方法分析家系相关细胞对之间的核定位的时间动态模式，发现模式相似性的大小随压力强度而增加，并在最高压力水平下被后代细胞强烈遗传。通过剖析长期范围内不同调制方案对一般压力响应动力学的贡献，我们的工作提供了对哪些方案可能在优化压力环境中的适应性方面发挥作用的见解。使用信息论方法分析家系相关细胞对之间的核定位的时间动态模式，发现模式相似性的大小随压力强度而增加，并在最高压力水平下被后代细胞强烈遗传。通过剖析长期范围内不同调制方案对一般压力响应动力学的影响，我们的工作提供了对哪些方案可能在优化压力环境中的适应性方面发挥作用的见解。