FIGURE 5 from Dabrafenib Alters MDSC Differentiation and Function by Activation of GCN2

Dabrafenib induces broad transcriptional changes in MDSCs. A, Top, UMAP plot of the integrated scRNA-seq data from MDSC differentiated ± 1.5 µmol/L DAB, showing the 22 clusters defined by Seurat analysis. Bottom, UMAP plot of the integrated scRNA showing the 11 annotated lineage clusters. B, UMAP plot of the integrated scRNA-seq data from MDSCs showing RNA expression of selected myeloid markers. Scale represents normalized RNA expression. C, Heat map of the SCPA multivariate distribution analysis of genes associated with the Hallmark, Reactome, and Gene Ontology (GO) Biological process pathways. Pathways are representative top biological processes involved in myeloid cell and PMN differentiation, MAPK activation, ISR, UPR, proliferation and translation, cytokine signaling, and respiration metabolism. Left panel shows q-value for individual pathways in each cluster. Right panel shows the average q-value ±SD for the pathways included in the biological process indicated, for each annotated group. Higher q-values represent pathways with greater differences upon stimulation with DAB versus control. q-value is defined by SCPA as the square root of the log10(P-adjusted values) based on the Rosenbaum cross-match test.