Our approach combines transplantation of a single HSC with whole-genome sequencing to obtain the mutational landscape of stem cells, while also allowing us to assess the functional capacity of mutant HSCs (Fig. 4a). We carried out transplants with one or five Aldh2−/−Fancd2−/− HSCs (Fig. 4b). These stem cells rarely engrafted (with a frequency of 4.8%), contributed less to haematopoiesis and were myeloid-biased compared to controls (Fig. 4c–e). These results indicate that Aldh2−/−Fancd2−/− HSCs are severely functionally compromised and share features with aged HSCs21,22.
