Chromosomal aberrations in etoposide-treated ER-Hoxb8 cells of different Trp53 allelic states

We aimed to investigate how the allelic configuration of TP53 in hematopoietic stem and progenitor cells influences the maintenance of genomic stability. To this end, we generated murine hematopoietic progenitor lines by expressing Hoxb8 in bone marrow cells from Trp53-fl-R245W-GFP mice. This approach produced cell lines with inducible Trp53 missense mutations in either mono- or biallelic configurations at the endogenous locus, while non-induced cells retained wild-type Trp53. To assess the impact of these allelic states on genomic stability, we exposed both non-induced and induced cells to three consecutive cycles of high-dose etoposide treatment to induce DNA damage. After recovery, cells were expanded as single-cell colonies and subjected to whole genome sequencing to detect potential differences in genomic aberrations across the different Trp53 genotypes.