Fig. 5: Leukemogenic signature in Eµ-PRMT5/TCL1 splenic B cells differs from Eµ-TCL1 mice and resembles RT tumors. | Nature Communications

Fig. 5: Leukemogenic signature in Eµ-PRMT5/TCL1 splenic B cells differs from Eµ-TCL1 mice and resembles RT tumors.

From: Dysregulation of PRMT5 in chronic lymphocytic leukemia promotes progression with high risk of Richter’s transformation

Fig. 5

a Bulk RNA-sequencing performed on leukemic cells from the spleen of Eµ-TCL1 mice at 3 months (n = 2) and 6 months (n = 2) of age compared with Eµ-PRMT5/TCL1 mice at 3 months (n = 3) and 6 months (n = 2) of age. Variance is visualized via a principal component analysis plot. b DEG analysis from bulk RNA-sequencing in cells from (a) displayed via heatmap. c Comparative gene expression analysis of spleen cells from Eµ-PRMT5/TCL1 mice at 6 months of age compared to all other groups (from a) by log2FC in RNA-seq (x axis) and log2FC in ATAC-seq (y axis). Points represent gene-peak pairs. The plot represents genes exceeding a cutoff of log2 fold change in RNA-seq > |1|. d Differential alternative splicing events between Eμ-PRMT5/TCL1 and Eμ-TCL1 cells (from a) at 3 and 6 months. SE skipped exon, RI retained intron, MXE mutually exclusive exons, A5SS alternative 5’ splice site, A3SS alternative 3’ splice site. e ScRNA-seq analysis of spleen cells in Eµ-PRMT5/TCL1 (n = 4) and Eµ-TCL1 (n = 4) mice, visualized via UMAP and clustered according to K-means (n = 10). B cell (Cd19+, Ms4a1+, Cd79a+), T cell (Cd3+, Cd4+, Cd8+), Mono: monocyte (Cd14+, Itgam), and neutrophil (Cd177, Itgam) clusters were assigned as indicated, Supplemental Fig. 4E. Cell density is calculated as the 2d kernel density estimate mapped to color scale. f K-means clusters stratified by genotype. Clusters are distinguished by color and number. g Heatmap highlighting the top 50 enriched genes in clusters 5.6 and 5.1 in mice (from e), visualizing expression relative to other B-cell clusters. Gene expression across 100 genes is shown as the average Log10-transformed expression in splenic B-cell clusters. Genes associated with leukemia and lymphoma are highlighted. Source data are provided as a Source Data file. h Relative gene expression of CLL and RT-related genes in Eµ-PRMT5/TCL1 and Eµ-TCL1 spleen cells (from e). Violin plots demonstrate the relative distribution of expression in B cells with non-zero expression stratified by genotype and shown as the Log10-transformed expression. Log2-transformed fold changes were calculated from pseudobulk differential expression analysis comparing B-cell expression between models. Points represent individual cells.

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