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. 2023 Jan 19;55(2):232–245. doi: 10.1038/s41588-022-01280-z

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© The Author(s) 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Extended Data Fig. 4 — a. 2-dimensional Wright-Fisher style model of clone dynamics. The basal layer consists of a hexagonal grid of cells. At time zero, a small proportion of cells is mutant (red) and the rest wild type (gray). Cells in the next generation are picked from neighboring cells – for example the cells which can be placed in the outlined position in generation 2 are those marked with an X in generation 1. Mutant cells with higher fitness have a higher probability of generating daughters in the next generation and expand into large clones (Supplementary Note). b. Inferred induction proportion and inferred fitness values from ABC fitting to the lineage tracing data (Supplementary Note) for Notch1^−/− (red), Notch1^+/− (purple) and Notch1^+/+ (black) clones in the respective animals. Each dot shows an ‘accepted’ parameter set. A fitness of 1 (dotted line) is neutral. c. Distributions of acceptable values of the fitness parameter. Whiskers show the upper and lower bounds of the 95% credible interval, boxes show quartiles, center lines indicate medians of credible intervals. A fitness of 1 (blue dotted line) is neutral. d. Mean clone sizes from simulations of the parameters at the peak of acceptable distributions (see Supplementary note). Median and 95% confidence intervals of 100 simulations shown for the simulation curves. Mean ± standard error of mean are shown for the experimental data. e. Proportion of tissue covered by Notch1^−/− clones over time in simulations using the best-fit for Notch1^−/− fitness. Notch1^+/− is either assumed to be neutral (haplosufficient, green) or to have the best fitting fitness parameter to the experimental analysis of Notch1^+/− clones (haploinsufficient, orange). Curves show median and shaded areas show 95% confidence intervals of 100 simulations. f. Representative snapshot images at 100 days, 300 days and 3000 days from the simulations shown in e. On the left, Notch1^+/− cells are haploinsufficient (fitting to experimental data), on the right the Notch1^+/− cells are assumed to be haplosufficient (neutral fitness). Cells from each genotype are color coded. All images show the same number of cells/area of simulated tissue. See Supplementary Note.