Metformin (Met) induces γ-globin protein and RNA in a FOXO3-dependent manner. (A) The effect of Met treatment on HbF in HSPCs with FOXO3 knocked out using CRISPR/Cas9, as determined by representative HPLC. (B) Three aggregate experiments. (C) Western blot showing the effect of CRISPR/Cas9 editing on FOXO3 protein. (D) Quantification of the effect of CRISPR/Cas9 editing on FOXO3 expression. Error bar represents SD. ***P < .0001, **P < .001. KO, knockout; N.S, not significant.