Fig. 5.

TNF-Tg LMCs exhibit gene expression changes associated with known pathways of joint inflammation and arthritis. Differentially expressed genes of the lymphatic muscle cell (LMC) cluster (cluster 1 in Fig. 3) from wild-type (WT) vs tumor necrosis factor transgenic (TNF-Tg) mice are shown as a volcano plot (A). Each dot represents a single gene, and black dots showed no significant change from WT (false discovery rate (FDR) > 0.01, below grey line). The top 5 downregulated (fold-change < 0) and top 5 upregulated (fold-change > 0) in TNF-Tg LMCs are identified by blue dots with gene identifiers. Ingenuity pathway analysis (IPA) was performed on all genes represented in (A), and notably the gene pathway modifications (blue = decreased, orange = increased pathway score) ultimately centered on an increase in “Organismal death” (B). The top 10 most significantly modified canonical pathways (C) and associated inflammatory diseases (D) for TNF-Tg vs WT LMCs were identified, where trends of increased (red), decreased (blue), and unchanged (grey) activity patterns are shown. Specific gene expression patterns in TNF-Tg LMCs were identified for their significant involvement in the “Inflammation of joint” pathways, and representative genes most differentially expressed only in the LMC and vascular smooth muscle cell (VSMC) clusters are indicated: Mmp3 (LMCs 1.65, VSMCs 1.41 log₂ fold-change (log2FC) in E), Cxcl12 (LMCs 1.54, VSMCs 0.69 log2FC in F), and Ccl19 (LMCs 1.24, VSMCs 2.12 log2FC in G). Wilcoxon rank sum test was performed between the same cell types of WT and TNF datasets with an FDR < 4.77E−21 for all comparisons. Sample sizes: WT LMCs = 1433 cells, TNF LMCs = 552 cells, WT VSMCs = 751 cells, TNF VSMCs = 580 cells