Fig. 3: MEOX2 functions through transcriptional activation of the Notch signaling pathway in CL GSCs. | Nature Communications

Fig. 3: MEOX2 functions through transcriptional activation of the Notch signaling pathway in CL GSCs.

From: Combined targeting of glioblastoma stem cells of different cellular states disrupts malignant progression

Fig. 3

a The UMAP plot of 3028 CL GSCs annotated by four cellular states. b Proportion changes of four cellular states cells in 3028 CL GSCs transduced with MEOX2 sgRNA or control sgRNA. c Diagram depicting the screening workflow to identify the MEOX2 downstream mechanism. Created in BioRender. Wang, X. (2025) https://BioRender.com/f42j224. d Gene set enrichment analysis (GSEA) of Hallmark, KEGG, and Reactome gene sets after MEOX2 knockout in 3028 (CL) GSCs. Normalized enrichment score (NES) and p values are shown by heatmap. e Violin-box plots showing the notch signaling score (Hallmark and KEGG) of the GSCs scRNA-seq data comparing sgCONT (n = 7078) vs. sgMEOX2 (n = 3168). Data are aggregated from technical replicates. f KEGG pathway enrichment analysis of MEOX2 ChIP-seq peak genes. g Input or MEOX2 binding signals of NOTCH1, NOTCH2, JAG1, and PSEN1 from Chip-seq on 3028 (CL) GSCs. h NOTCH1 overexpression rescued MEOX2 knockdown-induced cell viability decrease in CL GSCs (n = 6). Data are mean ± SD. i Sphere formation of CL GSCs with shCONT, shMEOX2, or shMEOX2 plus NOTCH1 overexpression (n = 6). Data are mean ± SD. j IB analysis of SOX2 and ID1 levels in 3028 (CL) and RKI (CL) GSCs transduced with NOTCH1 shRNA or control shRNA. k Bioluminescence images of mice with orthotopic xenografts from luciferase-expressing 3028 (CL) cells, showing tumor growth under shMEOX2 or shMEOX2 + NOTCH1 treatment (left). Luciferase signal intensities are shown (right). Data are mean ± SD; n = 3 biologically replicates per group. l Kaplan–Meier survival curves of mice bearing intracranial tumors derived from 3028 CL GSCs (n = 6) from the three groups in (k). Statistics: d The nominal p-value was calculated based on GSEA. e Unpaired Student’s t-test for two-group comparison. h, i, k one-way ANOVA with Dunnett’s multiple-comparison test. l Log-rank test. e, i Box plots show median (center line), 25th–75th percentiles (box bounds), and whiskers extend to minimum and maximum values within 1.5 times the interquartile range. Images: j Representative blots (n = 3). Source data are provided as a Source Data file.

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