Cell cycle phase inheritance models to reveal biological oscillators that drive the cell cycle

Advances in time-lapse microscopy mean individual cells can be tracked as they move through the cell cycle and their lineage information obtained. In the literature, many interesting results have been revealed by analysing the correlation in interdivision time of various family pairs of cells. 

We introduce a general stochastic matrix model of abstract cell-cycle factors that are inherited from the mother to daughter cell. The model can be parameterised from measured correlations alone, and contains common models of cell cycle, replication and size control as special cases.

Using Bayesian inference, we fit the model to six lineage tree datasets of bacteria and mammalian cells from available literature. Our model gives a consistently good fit to the data, despite the model parameters being unidentifiable. This suggests that using interdivision time data alone is not sufficient to identify precise cell cycle control mechanisms. However, analysing the posterior distributions reveals oscillations driving the cell cycle. The frequencies of these oscillations can be attributed to underlying biological oscillators, such as circadian rhythm. This insight helps us to understand the factors that affect cell-to-cell variability in interdivision time.