Somatic mutations in single HSCs of healthy elderly human subjects and aged wild-type mice. (A-B) Estimated yearly mutation rate per mega base pairs (Mb) (A) and total number of somatic mutations (B) in each clonally expanded HSC isolated from healthy elderly human subjects (70 to 75 years of age; n = 6) and aged wild-type mice (24 months of age; n = 6). Middle line and error bars indicate mean and standard error of the mean values, respectively. ***P < .001; ****P < .0001, Welch’s t test. (C-D) Genomic distribution and mutation signature of somatic mutations in aged human and mouse HSCs are shown in panel C. Nonnormalized mutational patterns in the context of trinucleotides are shown in panel D. (E). Hierarchically clustered heatmap showing the frequency of the COSMIC single-base substitution signatures (version 2) from each individual mouse and human HSC-derived colony as indicated by the blue scale. A dendrogram for the colonies is shown on the top. No statistical difference in contribution of mutation signatures was observed between aged mouse and human HSCs (Welch’s t test).