Effect of increasing RBC chimerism on sickle physiology and hematopoiesis. The various physiologic parameters (y-axis) are plotted against peripheral blood percentage of donor Hb (x-axis). For panels A-G, sickle (0% donor Hb) and eGFP (100% donor Hb) controls are shown as ▴. Mice that received transplants are shown as •. (A) Hematocrit versus percentage of donor Hb in the peripheral blood. (B) Peripheral WBC versus percentage of donor Hb in the peripheral blood. (C) Reticulocyte percentage versus percentage of donor Hb in the peripheral blood. (D) Annexin-V binding versus percentage of donor Hb in the peripheral blood. (E) Urine osmolarity versus percentage of donor Hb in the peripheral blood. (F) sVCAM concentration versus percentage of donor Hb in the peripheral blood. (G) Spleen weight (as percentage of total body weight) versus percentage of donor Hb in the peripheral blood. (H) Spleen apoptosis versus percentage of donor Hb in the peripheral blood. Apoptosis was determined either by Annexin-V binding (•,▴) or terminal deoxyribonucleotide transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay (▴,▵). Sickle (0% donor Hb) and eGFP (100% donor Hb) controls are shown as ▴ and ▴ for the Annexin-V binding and TUNEL assays, respectively. Animals that received transplants are shown as • and ▵ for the Annexin-V binding and TUNEL assays, respectively. (I) Normalization of lymphomyeloid-erythroid (LM/E) ratio occurred only in mice with 100% donor Hb in the peripheral blood. Splenic LM cells (•,▴) were defined as CD45⁺/PI^-. Splenic E cells (▴,▵) were defined as Ter119⁺/PI^-. The percentage of total splenocytes that were LM or E (y-axis) is plotted against peripheral blood percentage of donor Hb (x-axis). Sickle (0% donor Hb) and eGFP (100% donor Hb) controls are shown as • (LM) and ▵ (E). Mice that received transplants are shown as ▴ (LM) and ▴ (E).