P53 loss fully rescues HSPC survival and hematopoiesis defects caused by CHD8 deletion. (A) Efficient deletion of CHD8 or P53 shown by western blot analysis in Chd8^−/−, P53^−/−, and Chd8^−/−P53^−/− BM progenitors. (B) Total cellularity of BM cells in WT, Chd8^−/−, P53^−/−, and Chd8^−/−P53^−/− mice after 6 days of pI/pC injections. *P < .05; ***P < .001. WT represents Chd8^F/FP53^F/F mice. (C) Flow cytometry of LSK and LK cells in WT, Chd8^−/−, P53^−/−, and Chd8^−/−P53^−/− BM. Representative dot plots and frequencies of the HSPC subpopulations in lineage⁻ cells are shown. (D) Absolute number of LSK and LK cells from WT, Chd8^−/−, P53^−/−, and Chd8^−/−P53^−/− mice after 6 days of pI/pC injections. **P < .01; ***P < .001. (E) Percentage of apoptotic (annexin V⁺; 4′,6-diamidino-2-phenylindole⁻) SLAM HSCs and LKs in WT, Chd8^−/−, P53^−/−, and Chd8^−/−P53^−/− mice. ***P < .001; **P < .01; *P < .05. (F) Percentage of CD45.2 cells at different time points in the PB after pI/pC injection in successfully reconstituted mice. (G) Percentage of CD45.2 BM progenitors in the transplant-recipient mice after 4 months of pI/pC injections. *P < .05; **P < .01; ns, not significant. (H) Heat map of all differentially expressed transcripts in WT, Chd8^−/−, P53^−/−, and Chd8^−/−P53^−/− LSK RNA sequencing.