Figure 4.
The erythroid progenitor balance in mice receiving transplants closely resembled the sickle mice not receiving transplants until complete replacement of the peripheral blood with donor RBCs occurred. (A) Representative flow cytometric analysis of RBC ontogeny in sickle and eGFP spleens. Red cell maturation was mapped by determining the relative proportions of Termed/CD71high (region I), Terhigh/CD71high (region II), Terhigh/CD71med (region III), and Terhigh/CD71low (region IV) cells.13 Representative density-contour maps show the splenic RBC progenitor balance from eGFP and sickle mice. (B) Comparison of regions I to IV from spleens of control sickle (▪) and eGFP (▦) mice and representative mice with either 90% (▤) or 100% (□) peripheral RBC chimerism. This analysis gives a vivid illustration of the similarity of mice with 90% RBC engraftment to sickle mice that did not receive transplants and demonstrates that correction of RBC progenitor balance occurred only after 100% replacement with donor RBCs. (C-D) In both bone marrow (C) and the spleen (D), the RBC progenitor balance did not resemble donor eGFP mice until complete replacement of the peripheral blood with donor RBC occurred. For clarity, the percentage of early RBC progenitors (regions I, II, and III) were combined (▴,▵) and compared with the percentage of mature RBC progenitors (region IV; •,▴). For individual mice that received transplants, the percentage of RBC progenitors in the bone marrow (C) or spleen (D) that resided in region I + II + III (▴) or IV (▴) was determined (y-axis) and plotted against the percentage of donor Hb in the peripheral blood (x-axis). Early RBC progenitors (regions I + II + III) in control sickle (0% donor Hb) or eGFP (100% donor Hb) mice are shown as [▵]. Mature RBC progenitors (region IV) in control sickle (0% donor Hb) or eGFP (100% donor Hb) mice are shown as •.