Figure 2. COVID-19 BALF FABP4⁺ and RA synovial TREM2⁺ macrophages share transcriptomic profiles and regulatory TAM receptor pathways.

(A) Venn diagram illustrating numbers of unique and shared marker genes of ST TREM2^hi and BALF FABP4⁺ macrophage clusters as described in Figure 1. Marker genes were identified prior to integration of data sets (19, 24) and were calculated using MAST, setting a minimum percentage of cells in clusters expressing each marker to 40%. Genes considered differentially expressed at P < 0.05 after Bonferroni correction. (B) Heatmap illustrating scaled, pseudobulk expression of shared upregulated marker genes from ST and BALF clusters indicated in A. (C) Split UMAP plots comparing BALF macrophage clusters in health, and in mild and severe COVID-19, illustrating changes in expression of the TAM receptors AXL and MerTK, with their respective preferred ligands GAS6 and PROS1. Intensity of purple indicates expression level. (D) Heatmap illustrating scaled, pseudobulk expression of TAM receptors and associated ligands by each BALF cluster, across patient groups. TAM receptors and their ligands were significantly differentially expressed in severe COVID-19 versus healthy tissues (P ≤ 0.005), with Bonferroni correction for multiple comparison, as confirmed by MAST.