By using paired single-cell RNA and ATAC sequencing, multiplexed imaging, and spatial transcriptomics, along with in vitro modeling of cell-extrinsic factor signaling, a recent study revealed that myeloid and T-cell-derived TNF-α, IFN-γ, and IL-1β were important drivers of pathogenic FLS subset heterogeneity in RA [69]. The gene discussed is TNF; the disease is rheumatoid arthritis.