(A) Kaplan-Meier survival curve of untreated (UNTR) and luspatercept-treated (LUSP) SCD mice (n = 9–12). (B) Average PB RBC, hemoglobin (HGB), and hematocrit (HCT) levels in untreated and treated mice (n = 4–7). (C) Giemsa staining of PB smears. Arrows mark sickling cells. Scale bars: 20 μm. (D) Proportion (%) of normal, sickling, and abnormal cells (n = 4–6 independent experiments). (E) Average percentage reticulocytes (n = 12) in PB. (F) Average percentage MFR reticulocytes (n = 5). (G) Flow plots of biotin-retaining cells in PB. (H) Quantification of percentage biotin-retaining cells on days 0 to 4 (n = 9–13). (I) Flow plots of PB erythroid cells and their mitochondrial content. (J) Quantification of percentage MitoTracker-positive cells (n = 4–5). (K) Flow plots of BM erythroid maturation (I, proerythroblasts; II, basophilic; III, polychromatic; IV, orthochromatic and reticulocytes; V, RBCs). (L) Quantification of percentage BM erythroid progenitors (n = 6). (M) Representative image of spleens. Scale bar: 0.5 cm. (N) Spleen weight as percentage body weight (n = 8–9). (O) Flow plots of splenic red pulp macrophages (RPMs). (P) Quantification of percentage RPMs (n = 5–6). (Q) Flow plots of CD11b⁺CD115⁺ cells, cMos, and pMos. (R) Quantification of percentage CD11b⁺CD115⁺ cells (n = 6). (S) Ratio of cMos versus pMos (n = 6). *P < 0.05; **P < 0.01; ***P < 0.001 by 2-way ANOVA with Tukey’s post hoc test for B and H, and 2-tailed Student’s t test for all others.