Reversible and noisy progression towards a commitment point enables adaptable and reliable cellular decision-making.
Reversible and noisy progression towards a commitment point enables adaptable and reliable cellular decision-making.
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DOI：
10.1371/journal.pcbi.1002273
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发表时间：
2011-11
影响因子：
4.3
通讯作者：
Süel GM
中科院分区：
文献类型：
--
作者：
Kuchina A;Espinar L;Garcia-Ojalvo J;Süel GM
细胞必须在波动的细胞外条件下做出可靠的决定，但也要足够灵活以适应这种变化。细胞如何通过细胞决策的动力学来协调这些看似矛盾的要求，人们知之甚少。为了研究这一问题，我们定量测量了模式生物枯草芽孢杆菌在孢子形成过程中单细胞的基因表达和蛋白定位。我们发现，产孢过程经过嘈杂和可逆的步骤，走向一个不可逆的全有或全无的承诺点。具体来说，我们观察到在孢子形成过程中细胞自主和自发的基因表达爆发和瞬时蛋白定位事件。基于这些测量，我们开发了数学种群模型来研究可逆性程度如何影响细胞决策。特别是，我们评估了可逆性对以下方面的影响：1)孢子形成过程中的可靠性，以及2)在不断变化的细胞外应激条件下的适应性。结果表明，可逆的进展使细胞对长期的环境波动保持反应。相反，不可逆承诺点支持细胞命运选择的可靠执行，这对短期压力的减少是稳健的。这种相反的动态行为（可逆和不可逆）的组合，因此在环境条件的大范围变化中，最大限度地提高了适应性和可靠性决策。这些结果表明，决策系统可能采用一般混合策略来应对不可预测的波动环境条件。细胞必须不断做出决定，以应对环境的变化。这些决定必须是不可逆的，以防止细胞恢复到不适合的细胞状态，但也必须是灵活的，以允许细胞在环境变化时恢复到以前的状态。利用单细胞延时荧光显微镜，我们发现这些看似矛盾的特性在枯草芽孢杆菌细胞向孢子形成的过程中共存。在种群数学模型的基础上，研究人员认为，在环境条件变化的大范围内，向不可逆决策发展的可逆过程分别优化了决策的适应性和可靠性。
Cells must make reliable decisions under fluctuating extracellular conditions, but also be flexible enough to adapt to such changes. How cells reconcile these seemingly contradictory requirements through the dynamics of cellular decision-making is poorly understood. To study this issue we quantitatively measured gene expression and protein localization in single cells of the model organism Bacillus subtilis during the progression to spore formation. We found that sporulation proceeded through noisy and reversible steps towards an irreversible, all-or-none commitment point. Specifically, we observed cell-autonomous and spontaneous bursts of gene expression and transient protein localization events during sporulation. Based on these measurements we developed mathematical population models to investigate how the degree of reversibility affects cellular decision-making. In particular, we evaluated the effect of reversibility on the 1) reliability in the progression to sporulation, and 2) adaptability under changing extracellular stress conditions. Results show that reversible progression allows cells to remain responsive to long-term environmental fluctuations. In contrast, the irreversible commitment point supports reliable execution of cell fate choice that is robust against short-term reductions in stress. This combination of opposite dynamic behaviors (reversible and irreversible) thus maximizes both adaptable and reliable decision-making over a broad range of changes in environmental conditions. These results suggest that decision-making systems might employ a general hybrid strategy to cope with unpredictably fluctuating environmental conditions. Cells must continuously make decisions in response to changes in their environment. These decisions must be irreversible, to prevent cells from reverting back to unfit cellular states, but also be flexible, to allow cells to go back to their previous state upon environmental changes. Using single-cell time-lapse fluorescence microscopy, we show that these seemingly contradictory properties coexist in Bacillus subtilis cells during their progression to spore formation. We suggest, on the basis of a mathematical population model, that reversible progression towards the irreversible decision to sporulate optimizes respectively adaptability and reliability of decision-making over a broad range of changes in environmental conditions.
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影响因子：
9.8
作者：
Eichenberger P;Fujita M;Jensen ST;Conlon EM;Rudner DZ;Wang ST;Ferguson C;Haga K;Sato T;Liu JS;Losick R
通讯作者：
Losick R
影响因子：
3.6
作者：
Barak, I;Behari, J;Youngman, P
通讯作者：
Youngman, P
影响因子：
64.5
作者：
BURBULYS, D;TRACH, KA;HOCH, JA
通讯作者：
HOCH, JA
DOI：
10.1073/pnas.1002499107
发表时间：
2010-05-04
影响因子：
11.1
作者：
Chastanet, Arnaud;Vitkup, Dennis;Losick, Richard M.
通讯作者：
Losick, Richard M.
影响因子：
16
作者：
Blake, William J.;Balazsi, Gbor;Collins, James J.
通讯作者：
Collins, James J.