Higher SCL levels upregulate Kit expression. (A) Bone marrow cells were infected with SCL-GFP or the empty GFP vector for 48 hours. Kit shRNA or a control scramble sequence was then delivered by lentiviruses for 24 hours. After puromycin selection for 48 hours, cells were then transplanted into irradiated hosts. Three weeks later, mice were challenged with 2 doses of phenylhydrazine (PHZ) over 4 days. (B) Bone marrow cells were analyzed for c-Kit expression, within the GFP+Lin– fraction. (C) Donor-derived reconstitution (GFP) in control mice (–PHZ) and PHZ-treated mice (+PHZ). Kit+Lin– cells and erythroid differentiation (TER119/CD71) were analyzed in the GFP+ fraction of PHZ-treated mice. (D) Model of a positive feedback loop between c-Kit and SCL. Ligand-activated c-Kit upregulates Scl expression. Higher SCL levels further activate Kit transcription and increase bone marrow reconstitution.