Fig. 3

Glioblastoma microglia have a downregulated homeostatic TGF-β pathway, tumor-derived danger signal sensing capacity, and disrupted host defense. a TGF-β is the key regulator for microglial homeostasis. In GIM, Tgfb1 and downstream signaling genes including Smad3 are significantly downregulated, indicating a disruption of homeostatic functions. b EV-GFP^pos microglia showed significantly reduced levels of 57% of microglial sensome genes compared to GFP^neg, indicating reduced capability of sensing of tumor cells and tumor-derived danger signals in EV-GFP^pos microglia. c Normalized read counts of Siglecs, involved in direct glioblastoma-microglial cellular interactions, showed significant downregulation of Cd33, Siglece, and Siglech in (GFP^pos) GIM, whereas only Siglec1 was upregulated. d Seven out of eight sensome genes involved in the sensing of metabolic signals were significantly downregulated in EV-GFP^pos microglia. e Matrix metalloproteinases (MMPs) were upregulated in GIM. Mmp12, Mmp13, and Mmp14 were significantly upregulated tumor supportive genes. f Genes involved in phagocytic activity in microglial cells were upregulated. Cd93 and Clec7a were significantly higher in EV-GFP^pos microglia than GFP^neg microglia. g Programmed death ligand 1 and 2 (Pd-l1 and Pd-l2) were significantly upregulated in tumor-associated microglia. Asterisk (*) indicates significant (multiple testing adjusted p value < 0.05) differential expression. Error bar represents the SEM, bar represents the mean, and dots display individual measurements (C-G n = 3)