Figure 2.
Igf2bp2 deletion decreases the expression of genes related to mitochondrial metabolism and protein synthesis in young myeloid-biased HSCs. Myeloid-biased HSCs (CD150highCD34−LSK) were isolated from young (3 months) and aged (range: 22-26 months) Igf2bp2+/+ and Igf2bp2−/− male mice. HSCs from individual mice were analyzed by RNA-seq (n = 4 mice per group). DEGs were identified by the DESeq2 R package (v1.28.1), using the Benjamini-Hochberg–adjusted P < .05 as a cutoff. In myeloid-biased HSCs from young Igf2bp2−/− vs Igf2bp2+/+ mice, 1421 DEGs were identified, compared with only 26 DEGs in myeloid-biased HSCs from old Igf2bp2−/− vs Igf2bp2+/+ mice. (A) Principal component analysis (PCA) found that the first PC separated the HSC transcriptomes based on age and that the second PC separated Igf2bp2 gene status in young mice, but not in the HSCs from old mice. (B) A Venn diagram depicting the number of upregulated (red circle) and downregulated (blue circle) DEGs in myeloid-biased HSCs of Igf2bp2−/− vs Igf2bp2+/+ from young (top) or old (bottom) mice. The DEGs in myeloid-biased HSCs of young Igf2bp2−/− vs Igf2bp2+/+ mice overlapped with 83 mRNAs (green circle) that had been identified to be directly bound by IGF2BP2 in brown fat.14 Note that mRNA species that are bound by IGF2BP2 exclusively overlapped the downregulated DEGs in myeloid-biased HSCs of Igf2bp2−/− vs Igf2bp2+/+ mice. (C) Bar graph depicts the top 10 GO terms enriched for downregulated DEGs in young Igf2bp2−/− mice vs Igf2bp2+/+ mice (Benjamini-Hochberg correction). The gene number enriched in each term is shown at the end of the bar. Asterisks highlight mitochondria metabolism (red) and protein synthesis-related (blue) GO terms. (D) The heat map shows the expression pattern of all DEGs included in GO terms related to mitochondria metabolism and protein synthesis, as marked by asterisks in panel C. The color scale indicates the expression level. The heat map includes 10 target genes that have been shown to be bound by IGF2BP2 in brown adipose tissue14 (green circle in panel B) including 8 genes related to mitochondrial metabolism (marked by yellow asterisks) and 2 genes related to protein synthesis (marked by purple asterisks). An analysis of variance was applied to compare the expression of genes shown in the heat map of young Igf2bp2−/− myeloid-biased HSCs with old Igf2bp2−/− myeloid-biased HSCs (P = .26); of young Igf2bp2+/+ myeloid-biased HSCs with old Igf2bp2+/+ myeloid-biased HSCs (P = .048); or of young Igf2bp2−/− myeloid-biased HSCs with old Igf2bp2+/+ myeloid-biased HSCs (P = .49). The Igf2bp2 deletion makes the expression profile of mitochondria metabolism and protein synthesis–related genes of young myeloid-biased HSCs more similar to that of old myeloid-biased HSCs.

Igf2bp2 deletion decreases the expression of genes related to mitochondrial metabolism and protein synthesis in young myeloid-biased HSCs. Myeloid-biased HSCs (CD150highCD34−LSK) were isolated from young (3 months) and aged (range: 22-26 months) Igf2bp2+/+ and Igf2bp2−/− male mice. HSCs from individual mice were analyzed by RNA-seq (n = 4 mice per group). DEGs were identified by the DESeq2 R package (v1.28.1), using the Benjamini-Hochberg–adjusted P < .05 as a cutoff. In myeloid-biased HSCs from young Igf2bp2−/− vs Igf2bp2+/+ mice, 1421 DEGs were identified, compared with only 26 DEGs in myeloid-biased HSCs from old Igf2bp2−/− vs Igf2bp2+/+ mice. (A) Principal component analysis (PCA) found that the first PC separated the HSC transcriptomes based on age and that the second PC separated Igf2bp2 gene status in young mice, but not in the HSCs from old mice. (B) A Venn diagram depicting the number of upregulated (red circle) and downregulated (blue circle) DEGs in myeloid-biased HSCs of Igf2bp2−/− vs Igf2bp2+/+ from young (top) or old (bottom) mice. The DEGs in myeloid-biased HSCs of young Igf2bp2−/− vs Igf2bp2+/+ mice overlapped with 83 mRNAs (green circle) that had been identified to be directly bound by IGF2BP2 in brown fat.14 Note that mRNA species that are bound by IGF2BP2 exclusively overlapped the downregulated DEGs in myeloid-biased HSCs of Igf2bp2−/− vs Igf2bp2+/+ mice. (C) Bar graph depicts the top 10 GO terms enriched for downregulated DEGs in young Igf2bp2−/− mice vs Igf2bp2+/+ mice (Benjamini-Hochberg correction). The gene number enriched in each term is shown at the end of the bar. Asterisks highlight mitochondria metabolism (red) and protein synthesis-related (blue) GO terms. (D) The heat map shows the expression pattern of all DEGs included in GO terms related to mitochondria metabolism and protein synthesis, as marked by asterisks in panel C. The color scale indicates the expression level. The heat map includes 10 target genes that have been shown to be bound by IGF2BP2 in brown adipose tissue14 (green circle in panel B) including 8 genes related to mitochondrial metabolism (marked by yellow asterisks) and 2 genes related to protein synthesis (marked by purple asterisks). An analysis of variance was applied to compare the expression of genes shown in the heat map of young Igf2bp2−/− myeloid-biased HSCs with old Igf2bp2−/− myeloid-biased HSCs (P = .26); of young Igf2bp2+/+ myeloid-biased HSCs with old Igf2bp2+/+ myeloid-biased HSCs (P = .048); or of young Igf2bp2−/− myeloid-biased HSCs with old Igf2bp2+/+ myeloid-biased HSCs (P = .49). The Igf2bp2 deletion makes the expression profile of mitochondria metabolism and protein synthesis–related genes of young myeloid-biased HSCs more similar to that of old myeloid-biased HSCs.

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