We measured changes in ligand-receptor signaling pathways between microglia, astrocytes, and oligodendrocyte cells using MultiNicheNet55. We identified three ligand-receptor pairs that signal from microglia to astrocytes with high downstream gene activity: IL1B-IL1R1, OSM-OSMR, and TNF-TNFRSF1A (Fig. 6I, see Supplementary Table 18 for all ligand-receptor pairs). These three pairs have been shown to work synergistically to induce pro-inflammatory cytokines in astrocytes.56 Predicted downstream target genes of IL1B-IL1R1 in astrocytes included C3, the widely used marker of reactive astrocytes, as well as bZIP family TFs FOSL1, XBP1, and CEBPD. We identified a single ligand-receptor pair from both astrocytes and microglia to oligodendrocytes with a high ligand activity: TGFB1-ITGB8 (Extended Data Fig. 10).
