Fig. 5: Transcriptome profiling reveals transformed B cells in Eµ-MTCP1 mice.

A Comparison of IGHV gene usage among Eµ-MTCP1 (founder Z36), Eµ-TCL1, and wildtype mice (n = 3 per group) demonstrated clonal tumor populations in Eµ-MTCP1 and Eµ-TCL1 mice. Visualized via pie chart, the percent tumor volume comprised by the dominant clone of each mouse shown in black. All minority clones are grouped and their percent contribution is visualized via gray-checkered pattern. Gene names of the top 10 IGH genes in order of abundance are presented in Supplementary Table S3. B Unbiased RNA-sequencing of splenic B-cells isolated from Eµ-MTCP1 (founder Z36), Eµ-TCL1, and wildtype mice (n = 3 per group) revealed distinct clustering of Eµ-MTCP1 (red) and Eµ-TCL1 (yellow) samples from wildtype mice (blue) as visualized by principle component analysis. 62% variance was observed along PC1, and 12% variance was observed along PC2. C The 100 most-variable genes from (B) visualized via heatmap. A majority of these significantly differing genes encode IGH genes (not shown for clarity—whole list of genes can be found in the source data). Genes listed on the y axis are arranged via hierarchical clustering using Euclidean distance measurements. Heat map scale is representative of normalized Log2 expression between all samples. D Euler diagram visualizing differentially expressed genes between Eµ-MTCP1 vs wildtype mice (left circle, pink) and Eµ-TCL1 vs wildtype mice (right circle, yellow). A significant overlap (2962/4572; 65%) in the number of differentially expressed genes compared to wildtype mice were shared between Eµ-MTCP1 and Eµ-TCL1 mice (middle overlap, orange). E Ingenuity pathway analysis (IPA) of significantly enriched genes (Log2FC > 2, p < 0.001) unique to Eµ-MTCP1 vs wildtype mice or Eµ-TCL1 vs wildtype mice. Rainbow color scale reflects –Log(p value) determined via Fisher’s exact test. Complete list of IPA terms and p values are available in the Supplementary File: source data. F Differential mRNA expression analysis of splenic B cells from Eµ-MTCP1 and Eµ-TCL1 mice visualized via volcano plot (n = 3 per group). Seventy-nine genes enriched in Eµ-MTCP1 mice (red) or Eµ-TCL1 mice (yellow) are shown (Log2FC > 2; p < 0.001). P value determined in DESeq2 via Wald test. Complete list of genes and p values are available in the Supplementary File: source data.