Gutierrez Heldder, Taghizada Bakhtiyar, Meneghini Marc D
Department of Molecular Genetics, University of Toronto, Toronto, ON, M5S 1A8, Canada.
Microb Cell. 2018 Oct 29;5(11):511-521. doi: 10.15698/mic2018.11.657.
Transient exposures to environmental stresses induce altered physiological states in exposed cells that persist after the stresses have been removed. These states, referred to as cellular memory, can even be passed on to daughter cells and may thus be thought of as embodying a form of epigenetic inheritance. We find that meiotically produced spores in the budding yeast possess a state of heightened stress resistance that, following their germination, persists for numerous mitotic generations. As yeast meiotic development is essentially a starvation response that a/alpha diploid cells engage, we sought to model this phenomenon by subjecting haploid cells to starvation conditions. We find also that haploid cells exposed to glucose withdrawal acquire a state of elevated stress resistance that persists after the reintroduction of these cells to glucose-replete media. Following release from lengthy durations of glucose starvation, we confirm that this physiological state of enhanced stress resistance is propagated in descendants of the exposed cells through two mitotic divisions before fading from the population. In both haploid starved cells and diploid produced meiotic spores we show that their cellular memories are not attributable to trehalose, a widely regarded stress protectant that accumulates in these cell types. Moreover, the transiently heritable stress resistant state induced by glucose starvation in haploid cells is independent of the Msn2/4 transcription factors, which are known to program cellular memory induced by exposure of cells to NaCl. Our findings identify new developmentally and nutritionally induced states of cellular memory that exhibit striking degrees of persistence and mitotic heritability.
短暂暴露于环境压力会使暴露细胞的生理状态发生改变，且在压力消除后这种改变仍会持续。这些状态被称为细胞记忆，甚至可以传递给子细胞，因此可以被视为一种表观遗传形式。我们发现，出芽酵母中减数分裂产生的孢子具有增强的抗逆状态，在萌发后，这种状态会在多个有丝分裂世代中持续存在。由于酵母减数分裂发育本质上是a/α二倍体细胞参与的饥饿反应，我们试图通过使单倍体细胞处于饥饿条件来模拟这一现象。我们还发现，暴露于葡萄糖剥夺环境下的单倍体细胞会获得一种增强的抗逆状态，在将这些细胞重新引入富含葡萄糖的培养基后，这种状态仍然持续。在长时间葡萄糖饥饿解除后，我们证实这种增强抗逆性的生理状态在暴露细胞的后代中通过两次有丝分裂得以传播，然后才从群体中消失。在单倍体饥饿细胞和二倍体产生的减数分裂孢子中，我们都表明它们的细胞记忆并非归因于海藻糖，海藻糖是一种广泛认为的应激保护剂，在这些细胞类型中会积累。此外，单倍体细胞中由葡萄糖饥饿诱导的短暂可遗传抗逆状态独立于Msn2/4转录因子，已知Msn2/4转录因子会编程由细胞暴露于NaCl诱导的细胞记忆。我们的发现确定了新的由发育和营养诱导的细胞记忆状态，这些状态表现出显著程度的持续性和有丝分裂遗传性。
