Figure 5.
Integrated single-cell transcriptomics and phenotype-based ex vivo drug profiling in AML with megakaryocytic differentiation. (A) Uniform Manifold Approximation and Projection (UMAP) plot of scRNA-seq data of AML with erythroid differentiation (patient AML-5). Cells are colored based on clusters, which are named with the help of the reference-based cell type classification method SingleR. (B) Dot plot of expression of selected erythroid differentiation markers, TFs regulating erythroid differentiation, proliferation and progenitor markers, and BCL-2 family genes in the indicated cell types in the scRNA-seq data of AML with erythroid differentiation (AML-5). CD marker names are shown in gray. Dot size indicates the percentage of cells of a cell type expressing the given gene, and average expression is shown as normalized and scaled log-transformed counts. Bar plot above shows the percentage of each cell type out of all cells. (C) UMAP plot of scRNA-seq data of AML with megakaryocytic differentiation (patient AML-1). Cell types identified using the reference-based method SingleR are colored as indicated in panel D. Cell types comprising less than 1% of total cells are labeled as “Other.” (D) Dot plot of expression of selected megakaryocyte differentiation markers, TFs regulating megakaryocytic differentiation, progenitor markers, and BCL-2 family genes in the indicated cell types in the scRNA-seq data of AML with megakaryocytic differentiation (AML-1) as in panel B. (E) UMAP plots of cells analyzed using flow cytometry-based drug profiling in the patient with AML with erythroid differentiation (AML-5). Cells from control (DMSO) and BCL-XL inhibitor-treated (A-1331852, 300 nM) conditions are shown, with 1000 cells sampled from each condition. (F) UMAP plots of cells analyzed using flow cytometry-based drug profiling in the patient with AML with megakaryocytic differentiation (AML-1). Cells from control (DMSO) and BCL-XL inhibitor-treated (A-1331852, 125 nM) conditions are shown, with 1000 cells sampled from each condition. (G) Viabilities (percentage of viable cells compared with DMSO control) of the clusters representing different cell types in the patients with AML with erythroid differentiation (AML-5) after treatment with indicated concentrations of A-1331852 and venetoclax were analyzed using flow cytometry-based drug profiling. Clusters are colored as in panel E. (H) Viabilities (percentage of viable cells compared with DMSO control) of the clusters representing different cell types in the patient with AML with megakaryocytic differentiation (AML-1) after treatment with indicated concentrations of A-1331852 and venetoclax analyzed using flow cytometry-based drug profiling. Clusters are colored as in panel F. DMSO, dimethyl sulfoxide.

Integrated single-cell transcriptomics and phenotype-based ex vivo drug profiling in AML with megakaryocytic differentiation. (A) Uniform Manifold Approximation and Projection (UMAP) plot of scRNA-seq data of AML with erythroid differentiation (patient AML-5). Cells are colored based on clusters, which are named with the help of the reference-based cell type classification method SingleR. (B) Dot plot of expression of selected erythroid differentiation markers, TFs regulating erythroid differentiation, proliferation and progenitor markers, and BCL-2 family genes in the indicated cell types in the scRNA-seq data of AML with erythroid differentiation (AML-5). CD marker names are shown in gray. Dot size indicates the percentage of cells of a cell type expressing the given gene, and average expression is shown as normalized and scaled log-transformed counts. Bar plot above shows the percentage of each cell type out of all cells. (C) UMAP plot of scRNA-seq data of AML with megakaryocytic differentiation (patient AML-1). Cell types identified using the reference-based method SingleR are colored as indicated in panel D. Cell types comprising less than 1% of total cells are labeled as “Other.” (D) Dot plot of expression of selected megakaryocyte differentiation markers, TFs regulating megakaryocytic differentiation, progenitor markers, and BCL-2 family genes in the indicated cell types in the scRNA-seq data of AML with megakaryocytic differentiation (AML-1) as in panel B. (E) UMAP plots of cells analyzed using flow cytometry-based drug profiling in the patient with AML with erythroid differentiation (AML-5). Cells from control (DMSO) and BCL-XL inhibitor-treated (A-1331852, 300 nM) conditions are shown, with 1000 cells sampled from each condition. (F) UMAP plots of cells analyzed using flow cytometry-based drug profiling in the patient with AML with megakaryocytic differentiation (AML-1). Cells from control (DMSO) and BCL-XL inhibitor-treated (A-1331852, 125 nM) conditions are shown, with 1000 cells sampled from each condition. (G) Viabilities (percentage of viable cells compared with DMSO control) of the clusters representing different cell types in the patients with AML with erythroid differentiation (AML-5) after treatment with indicated concentrations of A-1331852 and venetoclax were analyzed using flow cytometry-based drug profiling. Clusters are colored as in panel E. (H) Viabilities (percentage of viable cells compared with DMSO control) of the clusters representing different cell types in the patient with AML with megakaryocytic differentiation (AML-1) after treatment with indicated concentrations of A-1331852 and venetoclax analyzed using flow cytometry-based drug profiling. Clusters are colored as in panel F. DMSO, dimethyl sulfoxide.

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