Liver-specific E2f7/E2f8 double knockout (LKO) hepatocytes remained predominantly euploid after repopulation of FRGN (Fah–/–Rag2–/– IL-2 common γ chain–/– Nod background) livers. A: Approximately 300,000 hepatocytes from LKO mice (males, 4 months old) were transplanted into FRGN recipient mice (females, 2 months old) and subjected to 2-(2-nitro-4-trifluoro-methylbenzoyl)-1,3-cyclo-hexanedione (NTBC) cycling to promote liver repopulation by transplanted donor cells. After completed repopulation, livers that contained a mixture of fumarylacetoacetate hydrolase positive (FAH+) donor hepatocytes and FAH– host hepatocytes were isolated. Hepatocytes were cultured briefly to stimulate cell division, proliferating hepatocytes were arrested in metaphase, and chromosomes from individual cells were identified by G-banding. Karyotypes were determined for donor-derived, male LKO hepatocytes that were Y chromosome+. B: Chromosome number is shown for LKO-derived hepatocytes. Skewed chromosome counts (eg, hypodiploid, hypotetraploid) were infrequent. C: Chromosome (Chr) gains and losses were summarized relative to the euploid number of homologous chromosomes. Every row marks an individual cell, and each column corresponds to a different chromosome. Detailed karyotypes are provided in Supplemental Table S3. D: The percentage of aneuploid LKO hepatocytes was compared with the degree of aneuploidy in freshly isolated 4-month–old adult control and LKO hepatocytes, which were originally reported in Figure 3D. Data are expressed as means ± SEM (D). n = 4 mice; 20 cells karyotyped per mouse (A); n = 80 LKO-derived hepatocytes (B). ∗∗P < 0.01, ∗∗∗P < 0.001.