Fig. 6.

Setd2 deficiency leads to HSPC proliferation defects. a, b GSEA analysis of E2F3 target genes (a) and deoxyribonucleotide (dNTP) metabolic process (b) in Setd2 KO BM LSKs relative to WT control. c qPCR detection of dNTP metabolism-related genes in KO and WT BM LSKs at 4 weeks after pI–pC induction. d CFU assay of Setd2 KO Lin⁻ BM cells transfected with empty vector or Rrm2b. e Cell cycle analysis of BM FLT3⁻-LSKs (left) and FLT3⁺-LSKs (right) from WT and KO mice at 4 weeks after pI–pC induction by using Ki67 staining. n = 4. f Statistical comparison of absolute cell count of BM HSPCs between WT or KO group at day 20 after single-time 5-FU treatment. n = 5. g Proliferation potential analysis of BM FLT3⁻-LSKs (left) and FLT3⁺-LSKs (right) by in vivo BrdU administration at day 20 after single-time 5-FU treatment. n = 4. h Genome distribution of mutations (SNVs and indels) in KO BM cells at 8 months after pI–pC induction. i Percentages of distinct mutation type of SNVs in KO BM cells. j Measurement of the ROS level in WT and KO LSKs at 4 weeks after pI–pC induction by using CellROX Deep Red Reagent staining. k Genome distribution of CNVs in KO BM cells at 8 months after pI–pC induction. l, m GSEA analysis of NUP98-HOXA9 targets (l) and interferon gamma pathway (m) in 8 months-old KO BM LSK cells relative to WT group. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001