Long-term codepletion of NR4A1/3 leads to a chronic activation of HSC cell cycle and reduced bone marrow cellularity. (A) Bone marrow cellularity at 4 and 8 weeks after NR4A1/3 codepletion. (B) Flow cytometry analysis of HSPC populations at 8 weeks after tamoxifen treatment. (C) Ratio of absolute counts of HSPC populations between CDKO and control mice at 4 and 8 weeks after NR4A1/3 codepletion. The red line represents 1:1 ratio. (D) BrdU analysis after a 16-hour BrdU uptake in HSPCs after an 8-week NR4A1/3 codepletion. (E-H) Flow cytometry analysis at 8 weeks after tamoxifen treatment of (E) early myeloid and lymphoid progenitors, (F) myeloid, (G) B cells, and (H) erythroid bone marrow cells. (I) Ratio of absolute counts of lineage-committed bone marrow cells between CDKO and control mice at 8 weeks after NR4A1/3 codepletion. The red line represents 1:1 ratio. Results expressed as mean ± SD, n = 3 to 5 mice per group. *P ≤ .05; **P ≤ .01; *** P ≤ .001.