From bacteria to humans, individual cells within isogenic populations can show significant variation in stress tolerance, but the nature of this heterogeneity is not clear. To investigate this, we used single-cell RNA sequencing to quantify transcript heterogeneity in single Saccharomyces cerevisiae cells treated with and without salt stress to explore population variation and identify cellular covariates that influence the stress-responsive transcriptome. Leveraging the extensive knowledge of yeast transcriptional regulation, we uncovered significant regulatory variation in individual yeast cells, both before and after stress. We also discovered that a subset of cells appears to decouple expression of ribosomal protein genes from the environmental stress response in a manner partly correlated with the cell cycle but unrelated to the yeast ultradian metabolic cycle. Live-cell imaging of cells expressing pairs of fluorescent regulators, including the transcription factor Msn2 with Dot6, Sfp1, or MAP kinase Hog1, revealed both coordinated and decoupled nucleocytoplasmic shuttling. Together with transcriptomic analysis, our results suggest that cells maintain a cellular filter against decoupled bursts of transcription factor activation but mount a stress response upon coordinated regulation, even in a subset of unstressed cells.

从细菌到人类，同基因种群内的单个细胞在压力耐受性上可能表现出显着差异，但这种异质性的性质尚不清楚。为了对此进行研究，我们使用单细胞RNA测序来定量酿酒酵母中的转录本异质性。用或不用盐胁迫处理的细胞探索种群变异并鉴定影响胁迫响应转录组的细胞协变量。利用酵母转录调控的广泛知识，我们发现单个酵母细胞在应激之前和之后均存在明显的调控变异。我们还发现，细胞的一个子集似乎以与细胞周期部分相关但与酵母超微生物代谢周期无关的方式使核糖体蛋白基因的表达与环境胁迫反应脱钩。表达成对的荧光调节剂的细胞的活细胞成像，包括具有Dot6，Sfp1或MAP激酶Hog1的转录因子Msn2，揭示了核仁穿梭的协调和解耦。连同转录组分析，