Fig. 7.

In-phase gating of cell cycle and apoptosis pathways by the circadian clock. a Analysis of correlations in IMT generated by the model with no circadian gating and b with circadian gating of both the cell cycle and apoptosis pathways. c Analysis of correlations in apoptosis times (AT) generated by the model with no circadian gating and d with circadian gating of both the cell cycle and apoptosis pathways. Note that the high correlations observed in d cannot be obtained with a model that has only circadian gating of the cell cycle, and no coupling to cell death (see Supplementary Figure 11). In a–d the dashed lines represent the 95% confidence intervals of the respective correlations as calculated from the data while the boxplots represent the 1st, 2nd, and 3rd quartiles of the lineage correlations generated from 25 simulation runs. The fraction of simulation runs resulting in correlation values within the 95% confidence intervals remains approximately the same when increasing the number of simulations from 25 to 150 in b and d. e Two extreme examples of completely in phase gating (top) and completely out of phase gating (bottom) of the cell cycle and apoptosis pathways. The curves represent the parameter μ of the EMG function. Blue represents μ for cell division while yellow is the corresponding μ for cell death. Note that increasing μ corresponds to decreasing risk, for both division and death. f Effect of increasing the phase difference Δφ between gating of cell cycle and cell death pathways on the sister correlations in IMT. The concentric rings indicate correlation levels and the blue bars denote the median correlations in IMT generated from 25 simulation runs, for different values of Δφ. Parameters used to generate the simulated results are given in Supplementary section 6