Fig. 3: Increased Chromatin accessibility and promoter hypomethylation drives STING expression across meningioma subtypes.

A UMAP cluster analysis of all cells within the meningioma microenvironment distinguishes distinct populations of meningioma, fibroblast, and extracellular matrix (ECM)-producing meningioma cells (n = 22 patients). Cell annotation was based on differentially expressed genes (DEGs) using standard parameters in Seurat FindAllMarkers on all clusters (B) Dot-plot demonstrating immune target expression analysis across meningioma cell populations, including the expression of STING (TMEM173) in meningioma, myeloid, and endothelial cells. Bubble size corresponds to the percent of cells expressing each marker; colors indicate average expression. C STING (orange) is widely expressed in the meningioma microenvironment, specifically in the neoplastic (SSTR2⁺), endothelial (CD31⁺), and myeloid (CD163⁺) populations. The bottom images also show the nuclear expression of pIRF3 (green) - a marker of downstream STING activation in meningioma, endothelial, and myeloid cells. n = 4 patients with similar results. D Pseudo-bulk ATAC-seq signal across myeloid and tumor cell populations from meningiomas reveals active chromatin regions near the STING locus (light blue highlight). Similar activation is seen in myeloid populations from glioma (GSE230389)¹⁰⁰; however, the chromatin near STING is closed in the glioma tumor populations. In the middle, a heatmap depicts the correlation of methylation position with expression in meningioma (top heatmap rows) and glioma (bottom heatmap rows). Significant correlations are indicated by “X” in correlation rows (FDR < 0.05). The strongest methylation probe correlating with STING expression is highlighted (red, bold, italicized): cg16983159. E Correlation of cg16983159 methylation level with STING expression among meningioma (n = 584 patients) and glioblastoma (n = 170 patients) samples, highlighted in green and grey, respectively. Two-sided Pearson correlation was used.