Fig. 5: MEOX2 and SRGN regulate the resistance of CL and MES GSCs to macrophage phagocytosis, respectively.

a Stacked bar plots indicate the cell composition of CLlowMESlow (n = 109) and CLhighMEShigh (n = 109) GBM in the TCGA GBM dataset based on the single-cell-based deconvolution method, CIBERSORTx. b Comparison of the proportion of cell composition between CLlowMESlow (n = 109) and CLhighMEShigh (n = 109) GBM in the TCGA GBM dataset. c Correlation coefficient between CL-MES signatures and various types of immune cell signatures in TCGA GBM dataset (n = 528). d Heatmap of anti-phagocytosis genes expression between four cellular state8 GSC-like tumor cells in scRNAseq datasets. e Heatmap of anti-phagocytosis genes expression between three subtypes5 GSCs in GSCs RNA-seq datasets (GSE119834). f Heatmap of anti-phagocytosis genes expression in MEOX2 knockout RNA-seq data. g Heatmap of anti-phagocytosis genes expression in SRGN knockout RNA-seq data. h Representative flow cytometry plots depicting the phagocytosis of GSCs transduced with shCONT, shMEOX2, shSRGN, or shMEOX2 + shSRGN co-cultured with macrophages. Created in BioRender. Wang, X. (2025) https://BioRender.com/f42j224. i Flow cytometry quantifies phagocytosis of CL + MES GSCs treated with shMEOX2, shSRGN, or dual treatment versus control. Data are presented as mean ± SD. n = 3 per group. j Experimental design to assess in vivo effects of combinatorial targeting of CL and MES on xenograft of mixed CL (3028) and MES (2907) GSCs. Created in BioRender. Wang, X. (2025) https://BioRender.com/f42j224. k Bioluminescence images show the effect of combined treatment with 75 mg/kg RG-4733 and 50 mg/kg PDTC every two days on tumor growth in mice bearing mixed CL and MES xenografts derived from luciferase-expressing 3028 (CL) and 2907 (MES) GSCs. Time points indicate days post-intracranial injection (left), with luciferase signal intensities shown (right). Data are presented as mean ± SD. n = 3 biologically independent mice per group. l, Kaplan–Meier survival curves for mice bearing subtype-mixed orthotopic tumors (3028 CL and 2907 MES) (n = 6) after combined treatment of 75 mg/kg RG-4733 every two days and 50 mg/kg PDTC every two days. Statistics: b, i Unpaired Student’s t test for two-group comparison. k one-way ANOVA with Dunnett’s multiple-comparison test. l Log-rank test. Source data are provided as a Source Data file.