Fig. 4: Involvement of the CD14_EGR1 subset in tissue damage and its potential as a biomarker for the progression of scleroderma renal crisis.

a Gene set enrichment analysis (GSEA) of differentially expressed genes (DEGs) in the CD14_EGR1 subset using the Molecular Signatures Database (MSigDB). P-values were calculated using Fisher’s exact test, with Benjamini–Hochberg method for multiple comparison. b The feature plots of EGR1, IL1B, CCR1, and SGK1 in monocytes from SSc patients with SRC (SRC) or without SRC (SSc w/o SRC). c UMAP plots showing the monocytes, macrophages and cDCs from peripheral blood (left) and kidney (right) of a SSc patient (Patient ID: SSc−19) at the onset of SRC. d Balloon plot showing highly expressed genes in subpopulations shown in (c). e Feature plots showing EGR1 and THBS1 expression at the onset of SRC. f Cell trajectory analysis on the peripheral blood and kidney tissue cells at the onset of SRC. The red line on the UMAP plot represents the cell trajectory. The root node is marked with a circle. Each cell is colored according to each pseudotime. g GSEA of DEGs in CD14_EGR1 (left) and THBS1_Mac (right) subsets using transcriptional regulatory relationships unraveled by sentence-based text-mining (TRRUST) Transcriptional Factor 2019. P-values were calculated using Fisher’s exact test, with Benjamini–Hochberg method for multiple comparison. h Percentage of the CD14_EGR1 subset to the total monocytes in SSc patients classified by serum autoantibody status. Patients were stratified into four subgroups: ARA (+) SRC (n = 4), ARA (+) SSc w/o SRC (n = 5), ARA (−) SSc w/o SRC (n = 12). ARA, anti-RNA polymerase III antibody. Values represent means with SEM. P-values were calculated using two-sided Dunn’s multiple comparison test between ARA (+) SRC group and each of the other groups after Kruskal–Wallis test. i The violin plot of EGR1 expression in monocytes before SRC development (before), at SRC onset (onset), and after treatment (after). j Correlation between the percentage of the CD14_EGR1 subset to total peripheral monocytes and the modified Rodnan skin score (mRSS) or systolic blood pressure (sBP). Correlations and P-values were calculated using Spearman’s correlation coefficient (r) with a two-sided test. Source data are provided as a Source Data file.