Extended Data Figure 8.
The simulation study to understand potential stochasticity in the embryoblast formation. (see Methods, ‘A stochastic model of embryoblast formation’ for more details)
a, The expected distribution of VAF of early embryonic mutations in a stochastic model in which n cells (y-axis) are randomly selected as epiblasts from the 32-cell stage embryo. The size of circle is proportional to the relative frequency of mutations at each VAF.
b, The stochastic model estimates the number of founder epiblast cells and the timing (cell stage) of their commitment. The maximum likelihood is selection of 11 cells in 64-cell stage.
c, The VAF distribution of early embryonic mutations expected from the maximum likelihood stochastic model. The maximum likelihood estimation (MLE) and the posterior probability by a Bayesian approach are shown by green and purple curves, respectively. Our observation of the 163 early embryonic mutations is represented by the histogram.
d, Unequal contribution of the first two cells to ICM cells by direct observation of 12 mouse-embryos using inverted light-sheet microscope by Strnad et al., Nature Methods (2016) (ref. 19). Schematic diagram (cell phylogeny) is shown above the bar graph. We re-analysed their observation, counting the relative contribution to ICM (black dots indicate the observed asymmetry in each embryo). These unequal contribution levels ranged from 0.5:0.5 to 0.74:0.26 and the average was 0.6:0.4.