SETD1A protects mice from activation-induced lethality. (A) SCL-CreER^T+;Setd1a^F/F or SCL-CreER^T+;Setd1a^+/+ mice were injected twice with pI:C and 7 and 14 days later with 5-FU. TAM-induced depletion of Setd1a was conducted 2 to 4 weeks beforehand. (B) Dot plots show the activation of LT-HSCs 8 hours after pI:C injection, resolving LT-HSCs for the expression of Ki-67 and DAPI staining. (C) Plots summarize the distribution of LT-HSCs in cell cycle phases as determined using the staining shown in panel B. Data from 2 independent experiments were pooled. Mice were used 3 to 4.5 weeks after the last TAM treatment. Differences in comparison with Figure 4D may be due to the time gap between TAM induction and analysis.⁵⁰  (D) Plots showing cell numbers of LT-HSCs, ST-HSCs, and MPPs from SCL-CreER^T+;Setd1a^F/F and control mice 12 hours after pI:C (light circles) or PBS (dark circles) treatment. Data are pooled from 2 independent experiments. (E) Plots showing MFI of H2A.X labeling of LT-HSCs, ST-HSCs, and MPPs from SCL-CreER^T+;Setd1a^F/F and control mice 12 hours after pI:C (light circles) or PBS (dark circles) treatment. Data are pooled from 2 independent experiments. (F) Survival plot after pI:C and 5-FU treatment. Data are summarized from 2 independent experiments using 10 SCL-CreER^T+;Setd1a^F/F mice and 9 control mice.