Ppm1d loss impairs HSC fitness. (A) Schematic of engineered locus in Ppm1d^fl/fl mice (left) and genotyping polymerase chain reaction showing different allelic states (right). (B) Peripheral blood WBC, lymphocyte, Plt counts, and Hct of Ppm1d^fl/fl;MxCre⁺ or Ppm1d^fl/fl;MxCre⁻ mice treated with pIpC at age 10 weeks. (C) Bone marrow stem cell analysis of Ppm1d^fl/fl;MxCre⁺ or Ppm1d^fl/fl;MxCre⁻ mice approximately 1 year after pIpC treatment. (D) Schematic of competition experiment between Ppm1d^fl/fl;Vav-Cre⁺;Cd45.2 or Ppm1d^+/+; Vav-Cre⁺;Cd45.2 and wild-type (WT) Vav-Cre⁺;Cd45.1/2 control bone marrow cells transplanted into lethally irradiated Cd45.1 recipients. Cisplatin was dosed intraperitoneally at 4 mg/kg and sublethal irradiation was dosed at 2.5 Gy. (E-F) Peripheral blood (E) and bone marrow (F) CD45.2 chimerism of recipient mice from Ppm1d^fl/fl;Vav-Cre⁺;Cd45.2 and WT Cd45.1/2 competition experiment outlined in panel D. (G) Schematic of serial transplantation and irradiation experiment of Ppm1d^fl/fl;Vav-Cre⁺ or Ppm1d^+/+;Vav-Cre⁺ bone marrow cells. The irradiation group received 5 Gy. (H-I) Peripheral blood (H) and bone marrow (I) CD45.2 chimerism of primary transplant recipients of Ppm1d^+/+;Vav-Cre⁺ (gray) and Ppm1d^fl/fl;Vav-Cre⁺ (black) bone marrow cells. (J) Peripheral blood CD45.2 chimerism of secondary transplant recipients of Ppm1d^+/+;Vav-Cre⁺ (gray) and Ppm1d^fl/fl;Vav-Cre⁺ (black) bone marrow cells. Error bars show SEM, ∗P < .01, ∗∗P < .0001.