Stockwell Sarah R, Rifkin Scott A
Section of Ecology, Behavior, and Evolution, Division of Biological Sciences, University of California, San Diego La Jolla, CA, USA.
Section of Ecology, Behavior, and Evolution, Division of Biological Sciences, University of California, San Diego La Jolla, CA, USA
Mol Syst Biol. 2017 Jan 30;13(1):908. doi: 10.15252/msb.20167323.
When a cell encounters a new environment, its transcriptional response can be constrained by its history. For example, yeast cells in galactose induce GAL genes with a speed and unanimity that depends on previous nutrient conditions. Cellular memory of long-term glucose exposure delays GAL induction and makes it highly variable with in a cell population, while other nutrient histories lead to rapid, uniform responses. To investigate how cell-level gene expression dynamics produce population-level phenotypes, we built living vector fields from thousands of single-cell time courses of the proteins Gal3p and Gal1p as cells switched to galactose from various nutrient histories. We show that, after sustained glucose exposure, the lack of these GAL transducers leads to induction delays that are long but also variable; that cellular resources constrain induction; and that bimodally distributed expression levels arise from lineage selection-a subpopulation of cells induces more quickly and outcompetes the rest. Our results illuminate cellular memory in this important model system and illustrate how resources and randomness interact to shape the response of a population to a new environment.
当细胞遇到新环境时，其转录反应可能会受到其历史的限制。例如，处于半乳糖环境中的酵母细胞诱导GAL基因的速度和一致性取决于先前的营养条件。长期暴露于葡萄糖的细胞记忆会延迟GAL的诱导，并使其在细胞群体中高度可变，而其他营养历史则导致快速、一致的反应。为了研究细胞水平的基因表达动态如何产生群体水平的表型，我们根据细胞从各种营养历史状态转换到半乳糖时，蛋白质Gal3p和Gal1p的数千个单细胞时间进程构建了动态向量场。我们表明，在持续暴露于葡萄糖后，这些GAL传感器的缺失会导致诱导延迟，这种延迟不仅时间长而且具有变异性；细胞资源会限制诱导；双峰分布的表达水平源于谱系选择——一部分细胞诱导速度更快，并胜过其他细胞。我们的结果揭示了这个重要模型系统中的细胞记忆，并说明了资源和随机性如何相互作用，以塑造群体对新环境的反应。
