Kavli Institute of Nanoscience, Delft, The Netherlands.
Department of Bionanoscience, Delft University of Technology, Delft, The Netherlands.
Mol Syst Biol. 2020 Nov;16(11):e9245. doi: 10.15252/msb.20199245.
Dormancy is colloquially considered as extending lifespan by being still. Starved yeasts form dormant spores that wake-up (germinate) when nutrients reappear but cannot germinate (die) after some time. What sets their lifespans and how they age are open questions because what processes occur-and by how much-within each dormant spore remains unclear. With single-cell-level measurements, we discovered how dormant yeast spores age and die: spores have a quantifiable gene-expressing ability during dormancy that decreases over days to months until it vanishes, causing death. Specifically, each spore has a different probability of germinating that decreases because its ability to-without nutrients-express genes decreases, as revealed by a synthetic circuit that forces GFP expression during dormancy. Decreasing amounts of molecules required for gene expression-including RNA polymerases-decreases gene-expressing ability which then decreases chances of germinating. Spores gradually lose these molecules because they are produced too slowly compared with their degradations, causing gene-expressing ability to eventually vanish and, thus, death. Our work provides a systems-level view of dormancy-to-death transition.
休眠通常被认为是通过静止来延长寿命。饥饿的酵母形成休眠孢子，当营养物质再次出现时，它们会苏醒（发芽），但在一段时间后无法发芽（死亡）。休眠孢子的寿命和衰老方式尚不清楚，因为每个休眠孢子内发生了哪些过程以及发生了多少过程仍不清楚。通过单细胞水平的测量，我们发现了休眠酵母孢子是如何衰老和死亡的：在休眠期间，孢子具有可量化的基因表达能力，这种能力会在数天到数月内逐渐下降，直到消失，导致死亡。具体来说，每个孢子的发芽概率都不同，因为在没有营养物质的情况下，其表达基因的能力下降，这是由一个在休眠期间强制 GFP 表达的合成电路揭示的。基因表达所需的分子（包括 RNA 聚合酶）的数量减少，会降低基因表达能力，从而降低发芽的几率。由于与降解相比，它们的产生速度太慢，孢子逐渐失去这些分子，导致基因表达能力最终消失，从而导致死亡。我们的工作提供了休眠到死亡转变的系统水平视角。
