Extended Data Fig. 6: Clone-specific analysis of mutation rate and signatures using genetically engineered mouse model.

a, The experimental schema. Trp53 or Ppm1d mutant cells were transplanted with WT cells in 1:9 ratio. After the engraftment, recipient mice were treated with vehicle or cisplatin. Single-HSPC colonies were generated from bone marrow cells. Each colony was genotyped and analyzed by WGS with 30× depth to detect somatic mutations. The schematics in panel a are created with BioRender.com. b, Bar plot comparing the number of somatic SNVs between WT and Trp53 mutant cells with or without cisplatin treatment. Statistical significance was assessed using an unpaired, two-sided t test. c, Bar plot showing the mutation signature between WT and Trp53 mutant cells with or without cisplatin treatment. d, Bar plot comparing the number of somatic SNVs between WT and Ppm1d mutant cells with or without cisplatin treatment. Statistical significance was assessed using an unpaired, two-sided t test. e, Bar plot showing the mutation signature between WT and Ppm1d mutant cells with or without cisplatin treatment. f, Bar plot describing the numbers of colonies with or without CNAs. Statistical significance was assessed using a two-sided chi-square test. n.s., not significant.