SRA

Profound distinctions exist between fetal liver (FL) and adult bone marrow (BM) hematopoietic stem cells (HSCs) in many aspects. Previously we showed that efficient H3K4 methylation plays an essential role in the differentiation and long-term maintenance of adult hematopoietic stem cell. However, its role in fetal hematopoiesis is unknown. Here, we show that loss of Dpy30, a core subunit of Set1/Mll complexes that responsible for efficient global H3K4 methylation, in FL results in embryonic anemia as well as the accumulation of HSCs that are defective in multiple lineage reconstitution as shown in mixed chimera assays. Global gene expression analyses identified 21 genes co-downregulated by Dpy30 loss in FL and BM HSCs, among which we further demonstrate that Igdcc4 and Ntpcr are important for efficient colony formation capacity of both FL and BM HSCs in vitro. This study suggests that Dpy30 and certain Dpy30 targets are fundamentally important in regulating HSCs regardless of developmental stages, and that the identified common target genes may provide new insight into the molecular regulation of hematopoiesis. Overall design: Purified HSCs from E14.5 embryos of control and Dpy30 KO genotypes (3 litters containing both genotypes in each litter) were used to isolate total RNAs for standard RNA-seq.