Lymphoma B cells drive LepR⁺ MSC transcriptional reprogramming. (A) Uniform manifold approximation and projection (UMAP) plot of the scRNAseq data from endothelial and stromal cells of Rag^−/−γc^−/− mice untreated (Ctrl), injected with PBS (sham), or grafted with DOHH2 and euthanized at early (day 19) and late (day 40) time points (left). Heat map of the enrichment of mouse nonhematopoietic cell signature scores as previously defined by scRNA sequencing in steady-state C57BL/6 mice (right).²⁶ (B) Stacked bar plot representing, for each cluster, the proportion of cells coming from the 4 conditions (control, sham, Gr.Early, and Gr.Late). The last bar of the plot represents the distribution of all cells between the different experimental conditions. The unbalance between experimental conditions in each cluster was evaluated using maximum residual values from a χ² test. (C) UMAP plot of the subclustering of the 3 most unbalanced clusters (4, 0, and 1) after analysis of differential abundance using the differentially abundant sequencing (DA-seq) algorithm. Four LepR⁺ MSC subclusters were identified: MSC_Ctrl, MSC_Sh, MSC_Gr.Early, and MSC_Gr.Late. (D) Venn diagram of the differentially expressed genes between MSC_Gr.Late vs MSC_Gr.Early, MSC_Gr.Late vs MSC_Sh, and MSC_Gr.Early vs MSC_Sh (adjusted P value <.05; absolute value of log₂ fold change of >.25). (E) Heat map of scores from human FL LN stromal cell subcluster signatures (reprinted from Abe et al²¹; upper part), human FL-LSC signature (reprinted from Mourcin et al¹⁷; middle part), and BM-MSC clusters obtained from HDs and patients with MM (reprinted from de Jong et al²⁷; lower part), relative to the LepR⁺ MSC clusters identified by DA-seq.