Steady-state HSC-enriched populations do not depend on menin-MLL1 collaboration despite a reduction in shared target genes. LSK cells (A) or HSCs (B) (defined as LSK/CD48⁻/CD150⁺) are not reduced in double heterozygous BM. Men1 or Mll1 alleles were deleted by pI:pC injection and animals were analyzed 12 to 13 days after the first injection. (A) Controls include both Mx1-cre–negative and Mx1-cre;Men1^f/+ animals, whereas controls in panel B are Mx1-cre;Men1^f/+ (denoted as Men1^Δ/+). Data from 2 experiments were pooled and 8- to 12-week-old mice were analyzed (A, n = 8-12 animals per genotype, P = .1164; B, n = 4-6 animals per genotype, P = .1712). (C) LSK cell quantification in Men1-deficient (Men1^Δ/Δ) vs Men1-deficient;Mll1-heterozygous (Men1^Δ/Δ;Mll1^Δ/+) BM. Cells were produced as described previously, n = 5-6 animals per genotype, P = .1011 for the comparison between Men1^Δ/Δ and Men1^Δ/Δ;Mll1^Δ/+. (D) HSC quantification in Men1^Δ/Δ and Men1^Δ/Δ;Mll1^Δ/+ BM, n = 4-6 animals per genotype, P = .3451 for the comparison between Men1^Δ/Δ and Men1^Δ/Δ;Mll1^Δ/+ BM. Animals were 8 to 9 weeks old when analyzed. (E-F) Gene expression in Men1^Δ/Δ and wild-type Men1^f/f LSK cells. LSK cells were sorted from 10- to 12-week-old animals 9 days after the first pI:pC injection. Expression levels were normalized to Hprt1, n = 3-4 animals per genotype. Statistical significance was determined using the unpaired Student t test; error bars represent 95% confidence intervals; ***P ≤ .001; **P ≤ .01.