Figure 4.
E4-ECs in contact with T-ALL establish a maladapted niche and acquire TEC-like features. (A) Heat map of the top 50 up- and downregulated genes from single-cell RNA-Seq in ECs alone or after coculture with T-ALL elements in both RO2 and 3119 PDX models. (B) Heat map depicting the pathway activity levels determined using the PROGENy tool applied to single-cell RNA-Seq data of E4-ECs cultured alone or in coculture with 3119 and RO2 T-ALL cells. (C) Dot plot displaying expression levels for a set of genes of interest (DLL1, JAG1, CD34, ETS1, ETS2, IGFBP4, IGFBP7, CD63, CD9, and S100A10) in E4-ECs that were cultured alone or in coculture with RO2 and 3119 T-ALL elements. The dot size encodes the percentage of cells expressing each gene, and the color encodes the average expression level across all cells. Expression levels were measured using the log-normalized counts. (D) Circos plot of ligand-receptor interaction obtained through the CellPhoneDB package on the RO2 PDX model, based on the relative expression level measured by single-cell RNA-Seq. Only the significant associations between ligands and receptors (on either the T-ALL or the EC side) are depicted. (E) List of a set of genes commonly upregulated by tumor endothelial cells (TECs) (vs normal ECs) and by E4-ECs cocultured with T-ALL cells (vs cultured alone) (see panel F). The list of processes and functions involving each gene was derived from the NDEx Biological Network Repository. (F) Venn diagram showing a comparison of genes upregulated in TECs vs normal E4-ECs (green circle) and in educated vs naive E4-ECs (blue circle). P value was calculated using a hypergeometric test. (G) List of a set of genes up- or downregulated by E4-ECs and T-ALL cocultured vs cultured alone in common between the 2 PDX models (RO2 and 3119) (supplemental Figure 4I). The direction of the differences is color-coded (blue, downregulated; red, upregulated). The list of processes and functions involving each gene was derived from the NDEx Biological Network Repository. IL-2, IL-6, interleukins 2 and 6.

E4-ECs in contact with T-ALL establish a maladapted niche and acquire TEC-like features. (A) Heat map of the top 50 up- and downregulated genes from single-cell RNA-Seq in ECs alone or after coculture with T-ALL elements in both RO2 and 3119 PDX models. (B) Heat map depicting the pathway activity levels determined using the PROGENy tool applied to single-cell RNA-Seq data of E4-ECs cultured alone or in coculture with 3119 and RO2 T-ALL cells. (C) Dot plot displaying expression levels for a set of genes of interest (DLL1, JAG1, CD34, ETS1, ETS2, IGFBP4, IGFBP7, CD63, CD9, and S100A10) in E4-ECs that were cultured alone or in coculture with RO2 and 3119 T-ALL elements. The dot size encodes the percentage of cells expressing each gene, and the color encodes the average expression level across all cells. Expression levels were measured using the log-normalized counts. (D) Circos plot of ligand-receptor interaction obtained through the CellPhoneDB package on the RO2 PDX model, based on the relative expression level measured by single-cell RNA-Seq. Only the significant associations between ligands and receptors (on either the T-ALL or the EC side) are depicted. (E) List of a set of genes commonly upregulated by tumor endothelial cells (TECs) (vs normal ECs) and by E4-ECs cocultured with T-ALL cells (vs cultured alone) (see panel F). The list of processes and functions involving each gene was derived from the NDEx Biological Network Repository. (F) Venn diagram showing a comparison of genes upregulated in TECs vs normal E4-ECs (green circle) and in educated vs naive E4-ECs (blue circle). P value was calculated using a hypergeometric test. (G) List of a set of genes up- or downregulated by E4-ECs and T-ALL cocultured vs cultured alone in common between the 2 PDX models (RO2 and 3119) (supplemental Figure 4I). The direction of the differences is color-coded (blue, downregulated; red, upregulated). The list of processes and functions involving each gene was derived from the NDEx Biological Network Repository. IL-2, IL-6, interleukins 2 and 6.

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