Fig. 3: The spectrum of mtDNA mutations changes during cell reprogramming.

a Normalised heteroplasmic shifts (HS) estimated between 83 fibroblast cell lines and 141 derived iPSC lines. Normalised heteroplasmic shifts are shown on the left side of the y axis. mtDNA regions shown by different colours; the depth of shading represents the mutation rate of iPSC-specific variants and lost variants within each mtDNA region (shown on the right side of the y axis). Variants above the red lines were extreme shifts seen in iPSCs. Source data are provided as a Source Data file. b Distributions of the HS in different mtDNA regions. c Cumulative distributions of the HSs within each mtDNA region. P values were calculated using two-sided Fisher’s exact test. d Pathogenic mutations observed in this study. Different colours represent lost, iPSC-specific or shared mutations between fibroblast cell lines and derived iPSC lines. Blue triangles are HFs in fibroblasts and orange triangles are HFs in iPSCs. mtDNA regions shown at the bottom. e Trinucleotide mutational signature of heteroplasmic variants observed in fibroblasts, iPSCs, lost in fibroblasts, iPSC-specific and shared variants between fibroblasts and iPSCs. The bars represent the substitution rate, mutations from the H or L-strand are shown in different colours. P values were calculated using two-sided Fisher’s exact test. f Mutational signature of six categories (C > A, C > G, C > T, T > A, T > C & T > G) within each mtDNA region. The bars represent the relative frequency of each category. Mutations from the H or L-strand are shown in different colours. g Correlation between mutational signatures observed in this study with the cancer signatures. The gradients of circles correspond to correlation R² values. The sizes of circles correspond to the p values (larger circles have smaller P values). The names of cancer signatures are shown at the top.