Figure 6

Figure 6

Haploinsufficiency of Kdm6a promotes myeloid‐biased hematopoiesis through repressing socs3a and activating Jak/Stat3 signaling. A) Heatmaps showing the binding signals of ATAC at the promoter regions (TSS±2kb) in cd41:eGFP^low HSPCs at 3 dpf from WT control and kdm6a^+/− mutants. B) Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis based on genes with differentially accessible chromatin at promoter regions. C) Venn plot showing the overlap of genes with specific accessible chromatin at promoter regions and downregulated expression in kdm6a^+/− HSPCs. Genes for ATAC‐seq were assigned by differentially accessible chromatin at promoter regions. D) Genome browser tracks for ATAC enrichment signals across the socs3a locus in WT control and kdm6a^+/− mutants. E) qPCR analysis of socs3a expression in sorted HSPCs from WT control and kdm6a^+/− mutants at 3 dpf (n = 3, mean ± SD, Student's t test). F,G) WISH for runx1 F) and %phenotype distribution G) in WT control, kdm6a^+/− mutants, and kdm6a^+/− mutants with socs3a mRNA at 3 dpf (n = 4, mean ± SD, one‐way ANOVA). (H‐I) WISH for mfap4 H) and %phenotype distribution I) in WT control, kdm6a^+/− mutants, and kdm6a^+/− mutants with socs3a mRNA at 3 dpf (n = 4, mean ± SD, one‐way ANOVA). J) Enrichment plot of the STAT3 targets between differentially regulated genes in kdm6a^+/− HSPCs and their WT controls by GSEA. K) qPCR analysis of STAT3 targets including ddx21, c1qbp, and slc25a12 in cd41:eGFP^low HSPCs isolated from WT control and kdm6a^+/− mutant embryos (n  = 3, mean ± SD, one‐way ANOVA). (L‐M) WISH for lyz L) and %phenotype distribution M) in WT control, kdm6a^+/− mutants, kdm6a^+/− mutants with ruxolitinib, kdm6a^+/− mutants with static, and kdm6a^+/− mutants with baricitinib at 3 dpf (n = 3, mean ± SD, one‐way ANOVA). N,O) WISH for mfap4 N) and %phenotype distribution O) in WT control, kdm6a^+/− mutants, kdm6a^+/− mutants with ruxolitinib, kdm6a^+/− mutants with static, and kdm6a^+/− mutants with baricitinib at 3 dpf (n = 3, mean ± SD, one‐way ANOVA). *p <0.05; **p <0.01; ***p < 0.001.