American Society of Hematology

Figure 4.

$Figure 4. Loss of Ski is sufficient to upregulate TGF-β signaling and deregulate splicing in HSC. (A) Heatmap of scRNA-Seq from SLAM HSCs (94 cells). Each column represents a single cell and each row represents 1 gene. Top: Clusters and groups; right: key genes (supplemental Figure 3A). (B-C) Scatter plot displaying the FDR vs Z-score of individual biological processes enriched within the differentially expressed genes in Ski−/− HSCs compared with Ski+/+ HSCs. Each dot represents a biological process, and the dotted line indicates an FDR value of 0.05 (supplemental Figure 3B-C). (D) Comparative analysis of differential gene expression. Heatmap of conserved differential gene expression between SKI-high MDS patient samples (vs normal CD34+ controls) and Ski−/− HSCs (vs Ski+/+ HSCs). Each row represents a single gene; (right) key genes are annotated. (E) Comparative analysis of alternative splicing. Heatmap of alternative splicing events that are conserved between SKI-high MDS patient samples (vs normal CD34+ controls) and pseudobulk of single cells of Ski−/− HSCs (vs Ski+/+ HSCs). Each row represents a single gene; right: key genes are annotated. (F) Conserved alternative splicing examples: representative sashimi plots of the RBM5/Rbm5 and TRA2B/Tra2b loci. (G-I) Peripheral blood analysis of noncompetitive transplant recipients at 10 months posttransplant with Ski+/+ or Ski−/− FL cells. (G) Complete blood counts. (H) Quantitation of the fraction of peripheral blood reticulocytes as a percentage of all CD45– cells. (I) Representative peripheral blood smears (8 biological replicates per group). The scale bars represent 10 μm. (G-H) Data are displayed as mean ± SEM. *P < .05. MCV, mean corpuscular volume; RBC, red blood cell; WBC, white blood cell count.$

Loss of Ski is sufficient to upregulate TGF-β signaling and deregulate splicing in HSC. (A) Heatmap of scRNA-Seq from SLAM HSCs (94 cells). Each column represents a single cell and each row represents 1 gene. Top: Clusters and groups; right: key genes (supplemental Figure 3A). (B-C) Scatter plot displaying the FDR vs Z-score of individual biological processes enriched within the differentially expressed genes in Ski^−/− HSCs compared with Ski^+/+ HSCs. Each dot represents a biological process, and the dotted line indicates an FDR value of 0.05 (supplemental Figure 3B-C). (D) Comparative analysis of differential gene expression. Heatmap of conserved differential gene expression between SKI-high MDS patient samples (vs normal CD34⁺ controls) and Ski^−/− HSCs (vs Ski^+/+ HSCs). Each row represents a single gene; (right) key genes are annotated. (E) Comparative analysis of alternative splicing. Heatmap of alternative splicing events that are conserved between SKI-high MDS patient samples (vs normal CD34⁺ controls) and pseudobulk of single cells of Ski^−/− HSCs (vs Ski^+/+ HSCs). Each row represents a single gene; right: key genes are annotated. (F) Conserved alternative splicing examples: representative sashimi plots of the RBM5/Rbm5 and TRA2B/Tra2b loci. (G-I) Peripheral blood analysis of noncompetitive transplant recipients at 10 months posttransplant with Ski^+/+ or Ski^−/− FL cells. (G) Complete blood counts. (H) Quantitation of the fraction of peripheral blood reticulocytes as a percentage of all CD45^– cells. (I) Representative peripheral blood smears (8 biological replicates per group). The scale bars represent 10 μm. (G-H) Data are displayed as mean ± SEM. *P < .05. MCV, mean corpuscular volume; RBC, red blood cell; WBC, white blood cell count.

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