Figure 4
Figure 4. Jak2V617F expression and Tet2 loss cause distinct and nonoverlapping gene expression changes. (A) Dendrogram constructed from unsupervised hierarchical clustering of all 13 data sets from WT (n = 4), Tet2null (n = 2), Jak2VF (n = 3), and Jak2VF/Tet2null (n = 4) LSK cells using Pearson correlation. (B) Venn diagram depicting differentially expressed genes in LSK cells from Jak2VF, Tet2null, and Jak2VF/Tet2null mice (false discovery rate = 10%; minimum fold change relative to WT samples = 1.3). (C) Hierarchical clustering of expression profiles of all 12 data sets according to the 17 genes differentially expressed in either Jak2VF, Tet2null, or Jak2VF/Tet2null mice relative to WT controls. A red/blue color scale depicts normalized gene expression levels (red: high; blue: low). Dendrograms were constructed using Pearson correlation. (D) GSEA demonstrating enrichment for STAT5A target genes in Jak2VF and Jak2VF/Tet2null LSK cells but not in Tet2null LSK cells (top row: STAT5A targets UP; bottom row: STAT5A targets DOWN). (E) GSEA demonstrating enrichment of an HSC self-renewal signature in Tet2null and Jak2VF/Tet2null LSK cells but not in Jak2VF LSK cells. P values for each of the comparisons are indicated in the figure. NES, net enrichment score; n.s., not significant.

Jak2V617F expression and Tet2 loss cause distinct and nonoverlapping gene expression changes. (A) Dendrogram constructed from unsupervised hierarchical clustering of all 13 data sets from WT (n = 4), Tet2null (n = 2), Jak2VF (n = 3), and Jak2VF/Tet2null (n = 4) LSK cells using Pearson correlation. (B) Venn diagram depicting differentially expressed genes in LSK cells from Jak2VF, Tet2null, and Jak2VF/Tet2null mice (false discovery rate = 10%; minimum fold change relative to WT samples = 1.3). (C) Hierarchical clustering of expression profiles of all 12 data sets according to the 17 genes differentially expressed in either Jak2VF, Tet2null, or Jak2VF/Tet2null mice relative to WT controls. A red/blue color scale depicts normalized gene expression levels (red: high; blue: low). Dendrograms were constructed using Pearson correlation. (D) GSEA demonstrating enrichment for STAT5A target genes in Jak2VF and Jak2VF/Tet2null LSK cells but not in Tet2null LSK cells (top row: STAT5A targets UP; bottom row: STAT5A targets DOWN). (E) GSEA demonstrating enrichment of an HSC self-renewal signature in Tet2null and Jak2VF/Tet2null LSK cells but not in Jak2VF LSK cells. P values for each of the comparisons are indicated in the figure. NES, net enrichment score; n.s., not significant.

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