Fig. 5: Spp1 regulates perivascular–microglial interaction networks.

a, Expression level of selected ligands expressed by cell types known to express Spp1 (PVF and PVM), by cell type and genotype. Radius of dot is proportional to the percentage of cells expressing the gene; color is the scaled gene expression level. b, Predicted receptor genes for ligands represented in a, which show differential expression in microglia (receiver cells). Color represents the predicted interaction potential. c, Predicted target genes downstream of receptors identified in b, which show differential expression in microglia (receiver cells). Color represents the predicted regulatory potential. d, Expression of predicted receptor genes in microglia, by genotype. Radius of dot is proportional to the percentage of cells expressing the gene; color is the scaled gene expression level. e, Quantification of Tgfbr1 and Itgb5 mRNA levels expressed by P2Y12⁺ microglia assessed by smFISH-IHC in 6-month WT, Spp1^KO/KO, App^NL-F and App^NL-F·Spp1^KO/KO SLM. One datapoint represents average of 1 mouse, calculated from 3–7 individual P2Y12⁺ microglia per mouse from n = 3 animals examined over 1 independent experiment. P Values from two-way ANOVA. f, Quantification of NicheNet hits CD29 (Itgb1) and CD321 (F11r) on microglia (CX3CR1^highCD45⁺CD11b⁺ CD206⁻) isolated from hippocampal homogenates of 6-month WT, Spp1^KO/KO, App^NL-F and App^NL-F·Spp1^KO/KO animals. One datapoint represents one individual mouse (microglia) pooled from n = 3 mice from one experiment. P values from two-way ANOVA, Bonferroni’s multiple comparisons test (CD29). g, Flow cytometry profiles of the protein expression intensity of CD29 and CD321 on microglia of the four genotypes. Data are shown as mean ± s.e.m. See also Extended Data Fig. 6 and Supplementary Table 2.

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