Fig. 4

Population change of HBEGF+ fibroblasts. a Expression of CLIC5, PDGFD, BDH2, ENPP1, SLAMF8, IL1RN, GK, and JAK2 are shown in Vin plot using single-cell RNA-seq profiles. b The Pearson correlation between HBEGF and gene markers such as CLIC5 (Cor = 0.5917), PDGFD (Cor = 0.4276), BDH2 (Cor = 0.4415), ENPP1 (Cor = 0.4097), SLAMF8 (Cor = −0.5497), L1RN (Cor = −0.2266), GK (Cor = −0.3257), and JAK2 (Cor = −0.4875) is displayed on a dot plot. c Expression of CLIC5, PDGFD, BDH2, ENPP1, SLAMF8, IL1RN, GK, and JAK2 are displayed in boxplot using bulk RNA-seq profiles of healthy joint synovium (n =26), RA joint synovium (n = 53), and OA joint synovium (n = 33). Significance determined by Student’s t test (CLIC5, P = 0.0018, PDGFD, P = 0.0238, BDH2, P = 0.0001, ENPP1, P = 0.0399, SLAMF8, P = 0.0001, L1RN, P = 0.0602, GK, P =0.1461, JAK2, P = 0.0001). d Expression of CLIC5, PDGFD, BDH2, ENPP1, SLAMF8, IL1RN, GK, and JAK2 displayed in a boxplot using bulk RNA-seq profiles from RA synovium before and after triple DMARD treatment (n=19). Significance determined by Student’s paired t test (CLIC5, P = 0.0355, PDGFD, P = 0.0022, BDH2, P = 0.0010, ENPP1, P = 0.0124, SLAMF8, P = 0.0038, L1RN, P = 0.4620, GK, P =0.1461, JAK2, P = 0.0048). e UMAP projection of single-cell RNA-seq data of 28,983 cells from two mouse datasets. Seven clusters at UMAP of integrated dataset. f Expression of Hbegf shown in dot plot. g GSEA using top 200 expressed gene markers of each cell cluster in human synovium as gene sets and ranked gene lists from Hbegf+ fibroblasts in mouse synovium. Normalized enrichment scores of HBEGF+ fibroblasts, NES = 1.6723, P.adj = 0.0001. h Percentage of Hbegf+ fibroblasts in synovium under different states (health, STA, and STA after treatment)