Fig 1.
Normalization of the hematological panel of PV animals following Tmprss6-ASO treatment.
One month after bone marrow transplant (BMT) animals received Tmprss6-ASO or CTRL-ASO. Six weeks of Tmprss6-ASO administration led to the significant reduction in HCT (A) as well as Hb (B), and RBC (C) when compared with animals treated with CTRL-ASO and normalized when compared with experimental BMT-WT untreated animals. As expected MCV was significantly reduced (D) when compared with CTRL-ASO and BMT-WT animals but no changes were observed in MCH (E) and Spleen Size (F). For all the analyzes were used BMT-WT mice (n = 3), BMT-PV-CTRL-ASO mice (n = 6), and BMT-PV-Tmprss6-ASO mice (n = 7). Results represent mean ± SD. Bars represent standard deviation (SD). Asterisks refer to statistically significant differences: **P ≤ 0.01, *P ≤ 0.05.
Fig 2.
Tmprss6-ASO reduced erythropoiesis in the bone marrow of PV mice.
Flow cytometry analysis of bone marrow and spleen (A) showed signs of iron restricted erythropoiesis as indicated by decreased erythroblast maturation with a decreased ratio of enucleated:nucleated (E:N) cells, consistent with more ineffective erythropoiesis. Flow cytometry analysis of the five clusters of erythroid populations shows significant evidence of decreased erythroblast differentiation in the BM (orthochromatic erythroblasts /reticulocytes, and mature red cells) (B), while only a trend can be appreciated in the spleen (mature red cells) (C). For these analyses were used BMT-WT mice (n = 3), BMT-PV-CTRL-ASO mice (n = 6), and BMT-PV-Tmprss6-ASO mice (n = 7). Results represent mean ± SD. Bars represent standard deviation (SD). 2-way ANOVA (with Tukey’s multiple comparisons tests) was used for the statistical analysis. Asterisks refer to statistically significant differences: ****P≤ 0.001, ***P≤ 0.005. Only statistical differences between BMT-PV-Ctrl-ASO and BMT-PV-Tmprss6-ASO mice are indicated in the graphs.