Fig. 3: Effect of TP53 disruption on de novo CA formation, and modelling basal CA rates. | Nature

Fig. 3: Effect of TP53 disruption on de novo CA formation, and modelling basal CA rates.

From: Origins of chromosome instability unveiled by coupled imaging and genomics

Fig. 3: Effect of TP53 disruption on de novo CA formation, and modelling basal CA rates.

a,b, Frequency of nuclear (a) and anaphase (b) phenotypes in MCF10A TP53−/− cells from long-term live-cell imaging. c, Observed CA frequency by cell (Fisher’s exact test). d, Fold change in CA numbers per cell for TP53−/− versus the respectively matched wild-type cell line model, shown across cell line models and nuclear phenotypes. e,f, Breakdown of CA classes in micronucleated MCF10A TP53−/− (e) and RPE-1 TP53−/− (f) cells, class percentage over all CAs. g, Agent-based model for estimating the de novo CA rate. Scheme representing available states (numbers in teal circles; 1, normal cell; 2, normal mitosis; 3, laggard mitosis; 4, bridge mitosis; 5, micronucleated cell) and available transitions (arrows) between states, with Pij being the empirically measured transition probabilities. Parameters are estimated for three mitosis types with R representing estimated CA rates. h, Mitosis type-specific CA rate estimations in MCF10 wild-type (WT) and TP53−/− models. Each data point represents the estimated value from an optimization run. Black lines represent the average weighted by the residual error of each optimized simulation.

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