The most striking change in Aldh2−/−Fancd2−/− HSCs was the presence of rearrangements that were not detected in most controls. Aldh2−/−Fancd2−/− stem cells contained on average two rearrangements per genome; in contrast, we observed only two large deletions among all ten control HSC genomes (Fig. 5k–l). In summary, these data provide the first whole-genome sequences obtained from single stem cells propagated in vivo. These stem cell genomes show that endogenous aldehydes induce a tapestry of inter-chromosomal changes that are mediated by mutagenic end-joining of DNA double-strand breaks.
