Patterns of interdivision time correlations reveal hidden cell cycle factors.
Patterns of interdivision time correlations reveal hidden cell cycle factors.
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DOI：
10.7554/elife.80927
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发表时间：
2022-11-15
期刊：
影响因子：
7.7
通讯作者：
Thomas P
中科院分区：
文献类型：
--
作者：
Hughes FA;Barr AR;Thomas P
细胞完成一轮细胞分裂所需的时间是一个随机过程，部分受细胞内因素控制。这些因素可以在细胞世代之间遗传，这在谱系树上不同家族关系的细胞之间的细胞周期定时中产生通常非直观的相关模式。在这里，我们制定了一个框架，隐藏的遗传因素影响细胞周期，统一已知的细胞周期控制模型，并揭示了三种不同的分裂时间相关模式：非周期性，交流发电机，振荡器。我们使用贝叶斯推理与细菌，哺乳动物和癌细胞中细胞分裂的单细胞数据集，以确定这些数据集的遗传基序。从我们的推断，我们发现，分裂间的时间相关模式不确定一个单一的细胞周期模型，但一般承认一个广泛的后验分布的可能机制。尽管这种不可识别性，我们观察到，推断的模式揭示了可解释的遗传动力学和隐藏的细胞周期因子的节律性。这表明细胞周期因子通常由昼夜节律驱动，但它们的周期在癌症中可能不同。因此，我们的定量分析表明，相关模式是一种影响细胞增殖的新兴现象，这些模式可能会在疾病中改变。
The time taken for cells to complete a round of cell division is a stochastic process controlled, in part, by intracellular factors. These factors can be inherited across cellular generations which gives rise to, often non-intuitive, correlation patterns in cell cycle timing between cells of different family relationships on lineage trees. Here, we formulate a framework of hidden inherited factors affecting the cell cycle that unifies known cell cycle control models and reveals three distinct interdivision time correlation patterns: aperiodic, alternator, and oscillator. We use Bayesian inference with single-cell datasets of cell division in bacteria, mammalian and cancer cells, to identify the inheritance motifs that underlie these datasets. From our inference, we find that interdivision time correlation patterns do not identify a single cell cycle model but generally admit a broad posterior distribution of possible mechanisms. Despite this unidentifiability, we observe that the inferred patterns reveal interpretable inheritance dynamics and hidden rhythmicity of cell cycle factors. This reveals that cell cycle factors are commonly driven by circadian rhythms, but their period may differ in cancer. Our quantitative analysis thus reveals that correlation patterns are an emergent phenomenon that impact cell proliferation and these patterns may be altered in disease.