Intracellular Energy Variability Modulates Cellular Decision-Making Capacity.
Intracellular Energy Variability Modulates Cellular Decision-Making Capacity.
复制标题
细胞内能量变异调节细胞决策能力。
DOI：
10.1038/s41598-019-56587-5
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发表时间：
2019
影响因子：
4.6
通讯作者：
Kerr R
中科院分区：
文献类型：
--
作者：
Kerr R
细胞在发育过程中以及在应对压力和变化的环境时都会产生表型多样性，从而有助于生存。从一系列表型选择中决定功能至关重要的细胞命运是由调控网络做出的，调控网络的动态依赖于基因表达，因此依赖于细胞能量收支(特别是ATP水平)。然而，尽管在生物系统中观察到明显的细胞间ATP差异，但能量可获得性对调控网络动态的影响经常被忽视，因为它是细胞决策的调节器，限制了我们对能量预算如何影响细胞行为的了解。在这里，我们考虑一个高度泛化的、依赖于ATP的决策调控网络的数学模型，并表明细胞间的ATP可变性改变了细胞可以做出的决策集。我们的模型表明，增加细胞内的能级可以增加支持的稳定表型的数量，相应地增加决策能力。具有亚阈值细胞内能量的模型细胞被限制为单一的表型，迫使采用特定的细胞命运。我们认为，细胞之间的能量差异可能是一个重要的考虑因素，以帮助解释在生物系统中观察到的细胞决策的可变性。
Cells generate phenotypic diversity both during development and in response to stressful and changing environments, aiding survival. Functionally vital cell fate decisions from a range of phenotypic choices are made by regulatory networks, the dynamics of which rely on gene expression and hence depend on the cellular energy budget (and particularly ATP levels). However, despite pronounced cell-to-cell ATP differences observed across biological systems, the influence of energy availability on regulatory network dynamics is often overlooked as a cellular decision-making modulator, limiting our knowledge of how energy budgets affect cell behaviour. Here, we consider a mathematical model of a highly generalisable, ATP-dependent, decision-making regulatory network, and show that cell-to-cell ATP variability changes the sets of decisions a cell can make. Our model shows that increasing intracellular energy levels can increase the number of supported stable phenotypes, corresponding to increased decision-making capacity. Model cells with sub-threshold intracellular energy are limited to a singular phenotype, forcing the adoption of a specific cell fate. We suggest that energetic differences between cells may be an important consideration to help explain observed variability in cellular decision-making across biological systems.