Figure 1.

Spontaneous Tak1 deletion in a small subset of hematopoietic stem progenitor cells (HSPCs) results in chronic bone marrow failure (BMF). Peripheral blood (PB) and bone marrow (BM) were collected from Tak1^mut mice and their WT and Cre⁺ littermates at age 14 months. (A) White blood cells (WBC), red blood cells (RBC), hemoglobin (Hb) and platelets (plt) were analyzed using Hemavet 950 Hematology System. (B) H&E-stained bone marrow section (tibia) after decalcification. (C) Number of total nucleated cells (TNCs) in BM from two hind limbs (four bones pooled: 2 tibias and 2 femurs from each mouse) were compared. (D) Representative flow cytometric plots for analysis of BM hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs). BM cells were first gated on Lin⁻ population and then analyzed for LK, LSK and LS populations. (E) Percentages of LK, LSK and LS populations in TNCs from BM. (F) Proliferation of Lin⁻c-kit⁺ HSPCs was compared among WT, Cre⁺ and Tak1^mut mice (14 months old) by BrdU pulse-labeling and flow cytometric analysis. (G) Death of Lin-c-kit⁺ HSPCs was compared among WT, Cre⁺ and Tak1^mut mice at indicated ages by Annexin-V staining followed by flow cytometric analysis. (I) Percentages of cells with ΔTak1 (Tak1 deletion) in Lin⁻ HSPCs, Lin⁺ differentiated BM cells and CD3⁺ T lymphocytes from Tak1^mut mice were determined by quantitative PCR. Lin⁻ HSPCs from WT mouse BM and Tak1^−/− leukemic cells (LCs) were used as negative and positive controls. *P<0.05 compared to WT and Cre⁺ mice.