Fig. 9

AICAR and SCT improve survival and alleviate dysfunction in Slc29a3^−/− mice. AICAR injection (500 mg/kg; SID) (n = 10/group) and SCT (1 × 10⁴ Slc29a3^+/+ HSCs and 5 × 10⁵ MSCs) (n = 16/group) extend the survival of Slc29a3^−/− mice (***P < 0.001; Mantel-Cox test) (a). AICAR-treated surviving mice show facial alopecia (insets; below), while both the AICAR and SCT groups show improved appearance and medullary hematopoiesis (right) (b). Changes in body weight (c), EchoMRI-measured fat and lean mass (d), absolute parametrial (PM) and inguinal (ING) fat pad mass (e), absolute soleus (SOL) and gastrocnemius (GA) skeletal muscle (SKM) mass (f) and bone marrow CFU-F frequency (g) in AICAR-treated surviving mice and SCT mice (n = 6, mean ± SEM). Clonogenicity (h) and marker expression (i) with serial passage of MSCs derived from SCT mice (n = 6, mean ± SEM). mRNA expression of transcription factors and markers after 14 (osteoblasts and adipocytes) and 28 (myocytes and chondrocytes) days of the differentiation of MSCs derived from SCT mice (n = 6, mean ± SEM) (j). Hematological parameters in AICAR-treated surviving mice and SCT mice. AICAR-treated surviving Slc29a3^−/− mice (n = 4, mean ± SEM) and SCT mice (n = 7, mean ± SEM) at 28 weeks are compared with saline-treated Slc29a3^−/− (n = 5, mean ± SEM) and WT mice (n = 6, mean ± SEM) at 12 weeks (k). Frequency of erythroid subpopulations within the bone marrow of AICAR-treated surviving mice and SCT mice (n = 6, mean ± SEM) (l). Cellularity (above) and HSC frequencies (below) in AICAR-treated (n = 5, mean ± SEM) and SCT mouse bone marrow (n = 7, mean ± SEM) (m). Culture expansion capacity (n) and percent of cells expressing HSC markers (o) with serial passage of SCT mouse bone marrow-derived HSCs (n = 6, mean ± SEM). CFU-forming capacity (above) and mRNA expression of transcription factors and markers (below) after 14 days of HSC differentiation in SCT mice (n = 6, mean ± SEM) (p). SCT, stem cell transplantation; CFU, colony-forming unit; CFU-F, CFU-Fibroblast; Hb, hemoglobin; PLT, platelet; LY, lymphocyte; MO, monocyte; NE, neutrophil; EO, eosinophil; ProE, proerythroblasts; EryA, early basophilic erythroblasts; EryB, late basophilic and polychromatic erythroblasts; EryC, orthochromatic erythroblasts/reticulocytes; GEMM, granulocyte, erythrocyte, monocyte, megakaryocyte; BFU-E, burst-forming unit-erythroid, colony-forming unit, CFU; CFU-M, CFU-macrophage, CFU-G, CFU-granulocyte; CFU-GM, CFU-granulocyte, macrophage. Statistical analyses were performed using ANOVA with Tukey’s multiple comparisons post-test and two-tailed Student’s t-test. *P < 0.05. Source data are provided as a Source Data file