Figure 6 from Phase Separation Mediates NUP98 Fusion Oncoprotein Leukemic Transformation

Abstract

<p>Expression of high FG motif valence NHA9 constructs in lin<sup>−</sup> HSPCs leads to hematopoietic cell transformation and aberrant expression of <i>Hox</i> family and other genes. <b>A,</b> Average number of colonies per 2,000 cells for lin<sup>−</sup> HSPCs expressing negative control empty vector and mEGFP-tagged NHA9 and mutant constructs. The values of colony numbers shown are mean ± SD from triplicate technical replicates of a representative experiment. <b>B–D,</b> RNA-seq was performed for lin<sup>−</sup> HSPCs expressing empty vector, G-NHA9, or mutants after 1 week of growth in methylcellulose containing myeloid and erythroid growth factors (<i>n</i> = 5 for each condition). <b>B,</b> Heat map for differentially expressed genes of interest. <b>C,</b> PCA of the 500 most variable genes. <b>D,</b> Gene set enrichment analysis for cells expressing G-NHA9, G-NHA9–8FA, or G-NHA9<sub>Midi</sub>—each versus empty vector. Pathways of interest are shown, with a complete list of significantly upregulated or downregulated gene sets in Supplementary Table S3. The most significantly dysregulated genes from each pathway are marked in <b>B</b>.</p>

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