Fig. 4.

Insulin like growth factor 1 (IGF1)-IGF1 receptor (IGF1R) ligand-receptor modulated microglia-astrocyte interaction. (A) Unbiased clustering of spatial transcriptomics (ST) spots. (B) t-distributed stochastic neighbor embedding (t-SNE) plot of nine clusters. (C, D) Spatial messenger RNA (mRNA) expression of Aif1 and glial fibrillary acidic protein (Gfap) in brain sections at 7 days post-injury (dpi). (E, F) Spatial mRNA expression of allograft inflammatory factor 1 (Aif1) and Gfap in different clusters at 7 dpi. (G) Top 30 differentially expressed genes (DEGs) in cluster 1. (H) Circos plot shows the genes which were related to at least one of the top 10 enriched functional clusters. (I) Heatmap shows the total number of interactions between cell types in the intracerebral hemorrhage (ICH) 7 dpi dataset obtained with CellPhoneDB. (J) Network diagram displays the intercellular communication between cell types in brain section at at 7 dpi. Each line represented the ligands expressed by the cell population, then the line connected to the cell types that expressed the cognate receptors. The loops indicated autocrine circuits. The line thickness represented the number of ligand-receptor pairs. (K) Dot plot showed the ligand-receptor pairs for each intercellular link. (L) Hotspots marked the locations where the IGF1-IGF1R ligand-receptor pair was more likely to occur in brain sections at 7 dpi, quantified by ligand-receptor interaction score. (M) Representative images of IGF1 and Iba1 double immunostaining show the reactive astrocytes and activated microglia around the lesion at 7 dpi. (N–P) Spatial mRNA expression of Igf1 in brain sections at 0, 7, and 21 dpi. Exp: expression; GO: Gene Ontology; MG: microglia; AS: astrocyte; Endo: endothelial cell; OL: oligodendrocyte; OPC: oligodendrocyte precursor cell; SGN: spiral ganglion neuron.