Supplementary Figure 13: SMARCD2 knockdown in human NB4 AML cells compromises myeloid pathways.

(a) Differentially expressed genes in undifferentiated AML-NB4 cells (shRNA-mediated SMARCD2 knockdown versus control) cluster in 11 groups by Reactome FI spectral partition and show significant enrichment for myeloid pathways. SMARCD2 is highlighted in red. Relevant pathways and interactions between pathways are indicated. The sources of pathway annotations are indicated in parentheses: C, CellMap; R, Reactome; K, KEGG; N, NCI PID; P, Panther; B, BioCarta. A complete list of the pathways enriched per cluster is given in Supplementary Table 6e. (b) Differentially expressed genes in ATRA-differentiated AML-NB4 cells (shRNA-mediated SMARCD2 knockdown versus control) cluster in 12 groups by Reactome FI spectral partition and show significant enrichment for myeloid pathways. SMARCD2 is highlighted in red. Relevant pathways and interactions between pathways are indicated. The sources of pathway annotations are indicated in parentheses: C, CellMap; R, Reactome; K, KEGG; N, NCI PID; P, Panther; B, BioCarta. A complete list of the pathways enriched per cluster is shown in Supplementary Table 6f. (c) Venn diagram of differentially expressed genes (undifferentiated and ATRA differentiated) and CEBPɛ target genes. Genes from all intersections are listed in Supplementary Table 6d. (d) Differentially expressed genes in ATRA-differentiated AML-NB4 cells overlap with CEBPɛ targets (21 genes) and interact via EP300, TP53, STAT1, and the ubiquitin system. Genes in green diamonds have been introduced as linker genes; differentially expressed genes are color-coded by continuous mapping of log(fold change) in SMARCD2-knockdown cells versus control cells (blue, reduced expression in SMARCD2-knockdown cells; red, increased expression in SMARCD2-knockdown cells). Analysis and display of the network were carried out with Cytoscape 3.3.0 and the Reactome Functional Interaction (FI) plugin: solid lines with arrows for activating/catalyzing FIs, solid lines with blocks for inhibitory FIs, solid lines (alone) for FIs extracted from complexes or inputs, and dotted lines for predicted FIs. This data set is derived from NB4 cells exposed to 1 μM ATRA for 2 d and, thus, cannot directly be compared to the qPCR data shown in Figure 5a.