TKO mice have fewer myeloid progenitor cells and more hematopoietic stem cells (HSCs), which can be rescued with a genetic cross to Ripk1(^+/−) heterozygous mice. (A) Flow cytometry analysis of bone marrow to examine LSK and (B) SLAM-HSC populations. Mice were examined before onset of sickness. Younger mice were 11 to 15 weeks old, and older mice were 15 to 20 weeks of age. Bid^+/+, n = 5; Bid^−/−, n = 5; DKO, n = 6; TKO younger, n = 5; and TKO older, n = 9. (C) Examination of the number of BrdU-positive SLAM-HSCs in bone marrow. Mice were injected with a total of 4 mg BrdU in 3 doses over 36 hours. Bone marrow was harvested, depleted for terminal lineages, and stained for flow cytometry. Mice were 18 to 20 weeks of age. (D) Numbers of myeloid progenitors (Lin⁻Sca-1⁻c-Kit⁺) as in panel A. Mice were 18 to 20 weeks of age. (E) Number of BrdU-positive myeloid progenitors. Numbers of mice for panels C–E are as follows: Bid^+/+, n = 8; Bid^−/−, n = 7; DKO, n = 8; and TKO, n = 7. (F) Western blot of Ripk1, cleaved Ripk1, and Ripk3 expression in Bid^+/+, TKO, and TKORipk1(^+/−) mouse bone marrow and spleen. (G) Intracellular flow cytometry analysis of LSK (left) and progenitor cell populations (right). TKO, n = 9; TKORipk1(^+/−), n = 6 . (H) Percentage of MPCs from lineage-depleted bone marrow. Bid^+/+, n = 12; TKO, n = 14; and TKORipk1(^+/−), n = 8. (I) Percentage of BrdU-positive myeloid progenitors from lineage-depleted bone marrow. Bid^+/+, n = 13; TKO, n = 15; and TKORipk1(^+/−), n = 8. (I) RBCs (10⁶/µL), hemoglobin (g/dL), and hematocrit (%) were measured in peripheral blood. Bid^+/+, n = 6; TKO, n = 6; and TKORipk1(^+/−), n = 6. ns, not significant; *P < .05, **P < .01, ***P < .001, and ****P < .0001. Data represent mean ± SEM.