Fig. 6: The Cxcr3 and Tlr1/2 pathways orchestrate the innate immune response shared among reactive glial cells. | Nature Communications

Fig. 6: The Cxcr3 and Tlr1/2 pathways orchestrate the innate immune response shared among reactive glial cells.

From: Shared inflammatory glial cell signature after stab wound injury, revealed by spatial, temporal, and cell-type-specific profiling of the murine cerebral cortex

Fig. 6

a Experimental scheme for single-cell RNA-sequencing of intact, stab wound-injured control (3/5 dpi_CTRL) and stab wound-injured inhibitor-treated (3/5 dpi_INH) cerebral cortices with the 10x Chromium platform. Red masked areas on brain schemes indicate biopsy areas used for the analysis. b UMAP embedding of integrated and batch-corrected single-cell transcriptomes of 55405 cells. Cells were distributed among 34 distinct clusters, color-coded, and annotated according to their transcriptional identities. c–e UMAPs illustrating subclustering of astrocytes (8 clusters) (c), microglia (8 clusters) (d), and oligodendrocytes (11 clusters) (e). Cells were further assigned to homeostatic (blue), or reactive (red) clusters according to cell origin (Supplementary Fig. 11). f Dot plots depict decreased expression of various shared inflammatory genes from Fig. 5c in the reactive glial clusters AG7, MG4, and OPCs2 after inhibitor treatment. g, h Shankey diagram of GO terms linked to glial subclusters illustrating common and unique downregulated biological processes in response to Cxcr3 and Tlr1/2 pathway inhibition at 3 dpi (g) and 5 dpi (h). Only the top 3 biological process GO terms (based on adjusted p-value) are illustrated for each glial subcluster and the entire list of GO terms is shown in Supplementary Data 7. Line width indicates the adjusted p-value. Significance was determined by performing GO enrichment analysis on gene sets. Data shown in this figure are derived from n = 12 intact animals over 3 independent experiments (5 scRNAseq libraries), n = 3 3dpi CTRL animals over 1 experiment (2 scRNAseq libraries), n = 3 3dpi INH animals over 1 experiment (2 scRNAseq libraries), n = 9 5dpi CTRL animals over 3 independent experiments (3 scRNAseq libraries) and n = 6 5dpi INH animals over 2 independent experiments (3 scRNAseq libraries). UMAP uniform manifold approximation and projection, dpi days post-injury, OPCs oligodendrocyte progenitor cells, COPs committed oligodendrocyte progenitors, MOL mature oligodendrocytes, VECV vascular endothelial cells (venous), VSMCs vascular smooth muscle cells, VLMCs vascular and leptomeningeal cells, BAM border-associated macrophages, NKT cells natural killer T cells, NA not available, CTRL stab wound-injured control animals, INH stab wound-injured inhibitor-treated animals.

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