scRNA-seq reveals a uniform transcriptional response across malignant cells. (A) Schematic overview of the scRNA-seq experiment. T-PLL (n = 3), T-LGL (n = 1), MCL (n = 3), and HCL (n = 2) samples were treated either with birinapant (200 nM), nutlin-3a (2500 nM), everolimus (200 nM), ibrutinib (100 nM), selumetinib (625 nM), or DMSO for 48 hours, followed by scRNA-seq. (B) Uniform manifold approximation and projection (UMAP) representation of scRNA-seq data. Cell types are indicated by color. Corresponding UMAP representation colored by treatment (C) and patient ID (D). (E) Donut plots showing the clonal composition based on T-cell receptor sequences of each T-PLL cluster and for healthy T-cells. Cells without available T-cell receptor sequence are shown in gray. Each clone is represented by a different color, the proportion of the donut area shaded indicates the size of the clone relative to all cells of the cluster. (F) Bar plots showing the number of significantly DEGs (FDR < 10%, |log2FC| > 0.25) relative to DMSO per cell type. An equal number of cells was randomly sampled for each combination of cell type and treatment. Upregulated genes are shown as red, downregulated genes as blue. Volcano plot showing the upregulated and downregulated genes of birinapant-treated T-PLL (G), healthy T cells (H), MCL (I), and HCL cells (J). An equal number of cells was randomly sampled for each combination of cell type and treatment. DEGs that are part of the TNF-α and NF-κB pathways are labeled.24-27 (K) Heat map showing expression changes of DEGs that belong to the TNF-α and NF-κB pathways,24-27 induced by ex vivo drug treatment with birinapant in the malignant cells of each patient sample compared with the matched DMSO negative control. Colors indicate the log2FC. (L) UMAP representation showing the malignant cells of patients with T-PLL; T-PLL1 (H371), T-PLL2 (H431), and T-PLL3 (H279); treated with birinapant or DMSO. Colors indicate the treatment (left) as well as the log-normalized expression of NFKBIA (right). ID, identity; h, hour; NFKBIA, NF-κB inhibitor alpha; p.adj., adjusted P value.

scRNA-seq reveals a uniform transcriptional response across malignant cells. (A) Schematic overview of the scRNA-seq experiment. T-PLL (n = 3), T-LGL (n = 1), MCL (n = 3), and HCL (n = 2) samples were treated either with birinapant (200 nM), nutlin-3a (2500 nM), everolimus (200 nM), ibrutinib (100 nM), selumetinib (625 nM), or DMSO for 48 hours, followed by scRNA-seq. (B) Uniform manifold approximation and projection (UMAP) representation of scRNA-seq data. Cell types are indicated by color. Corresponding UMAP representation colored by treatment (C) and patient ID (D). (E) Donut plots showing the clonal composition based on T-cell receptor sequences of each T-PLL cluster and for healthy T-cells. Cells without available T-cell receptor sequence are shown in gray. Each clone is represented by a different color, the proportion of the donut area shaded indicates the size of the clone relative to all cells of the cluster. (F) Bar plots showing the number of significantly DEGs (FDR < 10%, |log2FC| > 0.25) relative to DMSO per cell type. An equal number of cells was randomly sampled for each combination of cell type and treatment. Upregulated genes are shown as red, downregulated genes as blue. Volcano plot showing the upregulated and downregulated genes of birinapant-treated T-PLL (G), healthy T cells (H), MCL (I), and HCL cells (J). An equal number of cells was randomly sampled for each combination of cell type and treatment. DEGs that are part of the TNF-α and NF-κB pathways are labeled.24-27 (K) Heat map showing expression changes of DEGs that belong to the TNF-α and NF-κB pathways,24-27 induced by ex vivo drug treatment with birinapant in the malignant cells of each patient sample compared with the matched DMSO negative control. Colors indicate the log2FC. (L) UMAP representation showing the malignant cells of patients with T-PLL; T-PLL1 (H371), T-PLL2 (H431), and T-PLL3 (H279); treated with birinapant or DMSO. Colors indicate the treatment (left) as well as the log-normalized expression of NFKBIA (right). ID, identity; h, hour; NFKBIA, NF-κB inhibitor alpha; p.adj., adjusted P value.

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