Figure 4.
Figure 4. MLL-ENL induces changes in gene expression more efficiently in neonatal HPCs than in older or more committed progenitors. (A) Volcano plots show genes that are significantly induced (red) or significantly repressed (green) in HPCs, pGMs, or GMPs at P0, or in 10-week-old HPCs, after fetal MLL-ENL induction. The MLL-ENL transcript was mapped, and expression is indicated as a blue data point. RNA-seq data were analyzed, and adjusted (adj.) P values were calculated, as indicated in "Materials and methods." Genes that changed with an adjusted P < .05 were considered significantly differentially expressed. (B) Volcano plots showing a lack of differential gene expression after adult MLL-ENL induction. The panels indicate gene expression 6-month-old or 14-month-old mice (4 months or 12 months after doxycycline withdrawal). MLL-ENL was expressed at these ages as indicated by the blue dots. (C) Venn diagrams comparing the number of genes for the indicated cell types and ages that showed significantly increased expression and a fold change >2. Data reflect fetal MLL-ENL induction. FDR, false discovery rate. (D-G) Reads per kilobase of transcript per million mapped reads (RPKM) values for Hoxa9, Hoxa10, Mecom, and Igf1 at the indicated ages after fetal MLL-ENL induction. Error bars indicate standard deviation. ***Adjusted P < .001. For all groups, n = 3 to 4 independent biological replicates.

MLL-ENL induces changes in gene expression more efficiently in neonatal HPCs than in older or more committed progenitors. (A) Volcano plots show genes that are significantly induced (red) or significantly repressed (green) in HPCs, pGMs, or GMPs at P0, or in 10-week-old HPCs, after fetal MLL-ENL induction. The MLL-ENL transcript was mapped, and expression is indicated as a blue data point. RNA-seq data were analyzed, and adjusted (adj.) P values were calculated, as indicated in "Materials and methods." Genes that changed with an adjusted P < .05 were considered significantly differentially expressed. (B) Volcano plots showing a lack of differential gene expression after adult MLL-ENL induction. The panels indicate gene expression 6-month-old or 14-month-old mice (4 months or 12 months after doxycycline withdrawal). MLL-ENL was expressed at these ages as indicated by the blue dots. (C) Venn diagrams comparing the number of genes for the indicated cell types and ages that showed significantly increased expression and a fold change >2. Data reflect fetal MLL-ENL induction. FDR, false discovery rate. (D-G) Reads per kilobase of transcript per million mapped reads (RPKM) values for Hoxa9, Hoxa10, Mecom, and Igf1 at the indicated ages after fetal MLL-ENL induction. Error bars indicate standard deviation. ***Adjusted P < .001. For all groups, n = 3 to 4 independent biological replicates.

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