Extended Data Fig. 7: Interpretation of elderly adult HSPC phylogenies.

a, Plots illustrating the timing of acquisition of driver mutations and onset of clonal expansions respectively. These timings are inferred from the timing of the corresponding branches in the phylogenies depicted in Figs. 2, 3 and Extended Data Fig. 5. Bars are colours by gene mutation or blue for expanded clades with no known driver. Age 0 denotes the time of birth and black dots illustrate the age at sampling. b, Phylogenies created by randomly sampling 380 cells from the final full simulated population. As with the previous simulations, Nτ ~ population size because the time between symmetric self-renewal divisions is set at 1 year. In both simulated phyologenies the final population is 100,000 cells in size, but Phylogeny 2 has been created from a population that underwent a bottleneck in size to and Nτ of 10,000 cells between the ages of 35 and 50. This period of time over which the population size was reduced can be visualised in the blue box which highlights the increased density of coalescent events in this time block. The phylodyn trajectories are able to accurately recover information on changes in Nτ of the HSC population over time. c, Real HSC/MPP phylogeny for KX003 (81-year-male) with PB HSC/MPP terminal branches coloured red (BM HSC/MPP branches remain black). The CF of the largest clade is shown for PB and BM cells.