Single-Cell and Spatial Transcriptomics Reveals Selenoproteins Shape Immunosuppressive Microenvironment and Therapeutic Outcomes in Glioma

作者：Xiaowei Zhang, Na Zhang, Y Zhong, Siqi Ou, Guitao Wu, Taohui Ouyang, Kejun He · 发表于：Cancers · 年份：2026 · DOI：10.3390/cancers18091489 · 研究领域：Selenium in Biological Systems、Ferroptosis and cancer prognosis、Extracellular vesicles in disease

BACKGROUND: Gliomas exhibit substantial intratumoral heterogeneity, which limits prognostic precision and therapeutic efficacy. Selenoproteins are key regulators of redox homeostasis, but their role in glioma progression remains insufficiently defined. This study aimed to characterize glioma cells with high selenoprotein activity and to determine their biological and clinical significance. METHODS: We performed integrated multi-omic analyses combining bulk transcriptomic, single-cell transcriptomic, and spatial transcriptomic data to identify and characterize glioma cell states associated with elevated selenoprotein expression. Functional validation was conducted using SELENOS knockdown assays to evaluate effects on glioma proliferation, invasion, tumor growth, macrophage recruitment, CSF1 expression, and macrophage polarization. RESULTS: We identified a malignant glioma cell state, termed SehighMali, characterized by elevated selenoprotein expression and distinct metabolic and immunological features. SehighMali cells showed enhanced oxidative phosphorylation, MYC-associated transcription, and DNA repair activity, and preferentially engaged in immunosuppressive crosstalk with myeloid cells through the CSF1-CSF1R axis. Spatial analyses demonstrated enrichment of SehighMali cells in tumor cores and close colocalization with immunosuppressive myeloid populations. Across bulk cohorts, higher SehighMali abundance was associated with aggressive molecular features, poor clinical out...