Figure 4. Expression of AC3 Genes in PRIME Cells.

Panel A shows synovial cell subtype marker genes in clusters identified in blood. Enrichment scores of 200 single-cell RNA-seq (scRNA-seq) marker genes from 18 synovial subset cell types are shown. The dashed vertical line represents the threshold for significance (FDR <0.05, or −log₁₀ FDR >1.3). ABC denotes age-associated B cell, CTL cytotoxic T lymphocyte, IFN interferon, Tph/fh T peripheral helper/follicular helper, Treg T regulatory. Panel B shows the means of the standardized expression of genes that are common to synovial sublining fibroblasts (CD34+DKK+HLA−DRA+ fibroblasts) and AC3 in blood over the time to a flare (the dashed vertical line represents the start of a flare); I bars represent 95% confidence intervals. For standardization, the mean expression level for each gene was calculated across flares per week and then normalized across weeks. Panel C shows a Venn diagram of the numbers of AC3 genes that decreased during flares in the index patient (Patient 1) and the three additional patients (Patients 2, 3, and 4). Shading is used to highlight overlap between the index patient and the other patients. Panel D shows the log₂ relative expression ratio for AC3 genes in PRIME cells (flow-sorted CD45−CD31−PDPN+ cells) as compared with hematopoietic cells (flow-sorted CD45+) and in stained peripheral blood mononuclear cells (not flow sorted) as compared with hematopoietic cells (flow-sorted CD45+) as a technical control for the stress of flow sorting. The box-and-whisker plots indicate the median, interquartile range, and 1.5 times the interquartile range; the P value is from a Mann–Whitney U test.