Modeling the impact of single-cell stochasticity and size control on the population growth rate in asymmetrically dividing cells.
Modeling the impact of single-cell stochasticity and size control on the population growth rate in asymmetrically dividing cells.
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模拟单细胞随机性和大小控制对不对称分裂细胞群体增长率的影响。
DOI：
10.1371/journal.pcbi.1009080
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发表时间：
2021-06
影响因子：
4.3
通讯作者：
Amir A
中科院分区：
文献类型：
--
作者：
Barber F;Min J;Murray AW;Amir A
微生物种群在细胞生长形态和生命周期方面表现出惊人的多样性;然而，我们对这些因素如何影响细胞种群生长速率的理解仍然有限。我们使用理论和模拟来预测不对称细胞分裂，细胞大小调节和单细胞的随机性对人口增长率的影响。我们的模型预测，单细胞生长速率λ中的粗粒度噪声会降低群体生长速率，就像以前在对称分裂细胞中看到的那样。然而，对于λ中的给定噪声，我们发现不对称划分可以提高具有强尺寸控制的细胞的群体增长率（在“尺寸器”和“加法器”之间）。为了调和这一发现与丰富的对称分裂的生物在自然界中，我们建议，细胞生长和分裂的额外限制必须存在，这是不包括在我们的模型，我们探索其选定的扩展的影响。此外，我们发现，在我们的模型中，表观遗传遗传的世代时间可能会出现由于不对称分裂细胞的大小控制，提供了一个可能的解释，最近的实验观察芽殖酵母。总之，我们的研究结果提供了深入了解非典型生长形态所产生的复杂影响。单细胞生物种群的生长速度将对它们的长期成功产生重大影响。先前的工作表明，许多因素影响这种群体增长率，包括单细胞生长的速度，细胞之间的随机变异性，以及细胞是否调节自己的大小。在这里，我们表明，细胞分裂的不对称性也可以对人口增长率产生强烈的影响。我们使用理论和计算机模拟来研究不对称分裂的细胞的生长速率，每个细胞分裂事件产生一个较小的细胞和一个较大的细胞。我们发现，单细胞生长速度的变化仍然会降低群体的增长率，当不对称性是中等或大小控制是弱的，但细胞与强大的大小控制可以减少这种减少分裂更不对称。我们还表明，细胞周期的长度可以是正相关的密切相关的细胞时，他们都不对称分裂和调节其大小。这一反直觉的结果与先前基于对称分裂细胞中细胞大小调节的发现形成对比，如果细胞在一个细胞周期中生长“太长”，则这将通过在较短的后续细胞周期期间生长减少来校正。
Microbial populations show striking diversity in cell growth morphology and lifecycle; however, our understanding of how these factors influence the growth rate of cell populations remains limited. We use theory and simulations to predict the impact of asymmetric cell division, cell size regulation and single-cell stochasticity on the population growth rate. Our model predicts that coarse-grained noise in the single-cell growth rate λ decreases the population growth rate, as previously seen for symmetrically dividing cells. However, for a given noise in λ we find that dividing asymmetrically can enhance the population growth rate for cells with strong size control (between a “sizer” and an “adder”). To reconcile this finding with the abundance of symmetrically dividing organisms in nature, we propose that additional constraints on cell growth and division must be present which are not included in our model, and we explore the effects of selected extensions thereof. Further, we find that within our model, epigenetically inherited generation times may arise due to size control in asymmetrically dividing cells, providing a possible explanation for recent experimental observations in budding yeast. Taken together, our findings provide insight into the complex effects generated by non-canonical growth morphologies. How rapidly a population of single-celled organisms can grow will strongly impact their long-term success. Prior work has shown that many factors impact this population growth rate, including the rate at which single cells grow, random variability between cells, and whether cells regulate their own size. Here we show that cell division asymmetry can also have a strong impact on the population growth rate. We use theory and computer simulations to study the growth rate of cells that divide asymmetrically, producing one smaller cell and one larger cell with each cell division event. We show that variability in how fast single cells grow will still decrease the population growth rate, when asymmetry is moderate or size control is weak, but that cells with strong size control can diminish this decrease by dividing more asymmetrically. We also demonstrate that cell cycle lengths can be positively correlated for closely related cells when they both divide asymmetrically and regulate their size. This counter-intuitive result contrasts with previous findings based on cell size regulation in symmetrically dividing cells that if cells grow for “too long” in one cell cycle, this will be corrected for by reduced growth during a shorter, subsequent cell cycle.
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