LT-HSC-specific depletion of Setd1a is dispensable for survival but critically important for HSC function after transplantation. (A) Experimental outline for TAM treatment of SCL-CreER^T+;Setd1a^F/F or control mice and competitive transplantations using Lin⁻ BM cells. (B) Survival of TAM-treated SCL-CreER^T+;Setd1a^F/F or control mice (n = 6 each). (C) Blood parameters in SCL-CreER^T+;Setd1a^F/F and control mice 7 weeks after TAM treatment. Data are pooled from 5 (n = 16) independent experiments. (D) CD3⁺ T cells, B220⁺ B cells, and CD11b⁺ myeloid cells in the spleen of SCL-CreER^T+;Setd1a^F/F and control animals that have received TAM treatment 7 weeks before. (E) Numbers of LT- HSCs, ST-HSCs, and MPPs in SCL-CreER^T+;Setd1a^F/F or control mice that have received TAM treatment 7 weeks before. (F) Frequency of KSL cells in indicated mice. (G) Colony growth from SCL-CreER^T+;Setd1a^F/F or control (n = 7 each) total BM cells 7 weeks after TAM treatment. Data from 2 independent experiments are shown. (H) Blood donor cell chimerism after competitive transplantation of SCL-CreER^T+;Setd1a^F/F or SCL-CreER^T+;Setd1a^+/+ donor cells that were transplanted 7 weeks after TAM induction. (I) SCL-CreER^T+;Setd1a^F/F or SCL-CreER^T+;Setd1a^+/+ donor LT-HSCs 16 weeks after competitive transplantation. Data from 5 independent experiments are shown. HCT, hematocrit; M, myeloid cells; MCV, mean corpuscular volume; PLT, platelet.