MMP9 inhibitors increase the erythroid development in RPS14-deficient models. (A) Wild-type (WT) embryos stained with o-dianisidine showed strong brown signal on the yolk sac, indicating normal hemoglobin levels. rps14^−/− mutant embryos (MT) stained with o-dianisidine showed weak brown signal on the yolk sac, indicating reduced hemoglobin levels. MT treated with different concentrations of mmp9 inhibitors showed improved staining signal of hemoglobin compared with DMSO-treated rps14^−/− MT. All embryos are ventral views. (B-C) Human BMCD34⁺ cells were transduced with lentivirus carrying shRNAs against RPS14 or Luc control. After 1 day of transduction, cells were treated by MMP9 inhibitors. 9-I-L, MMP9-I 5 nM; 9-I-H, MMP9-I 1 μM; 9-II-L, MMP9-II 10 nM; 9-II-H, MMP9-II 10 μM. (B) Cells were sorted for GFP+ at 4 days after treatment. A total of 1500 GFP+ cells were plated in methylcellulose media specific for CFU-E colonies and cultured for 1 week. Colonies were counted by an investigator blinded to the conditions. (C) Cells were analyzed for the CD71 and the CD11b expression by using flow cytometry at 6 days after treatment with MMP9 inhibitors. Data are representative of 3 independent transduction experiments. *P < .05, **P < .01, ***P < .001. ERY media, erythroid media; MY media, myeloid media.