Single-cell and spatial atlas of glioblastoma heterogeneity: characterizing the PCLAF+ subtype and YEATS4’s oncogenic role

作者：Siqi Ma, Yuwei Sun, Shaowei Zheng, Yilong Fu, Liangyu Wang, Dun Liu, Henan Jiao, Xuqiang Zhu, Xueyuan Li, Dongming Yan, Di Chen, Zi Ye · 发表于：Frontiers in Immunology · 年份：2025 · DOI：10.3389/fimmu.2025.1614549 · 被引用次数：3 · 研究领域：Single-cell and spatial transcriptomics、Glioma Diagnosis and Treatment、Neuroinflammation and Neurodegeneration Mechanisms

Background Glioblastoma (GBM) was considered the most aggressive type of primary brain tumor, marked by poor clinical outcomes and a high tendency to relapse. The therapeutic efficacy of GBM was significantly compromised by tumor heterogeneity, dysregulated metabolic pathways, the formation of an immunosuppressive microenvironment, and treatment resistance. Therefore, multi-dimensional therapeutic strategies targeting GBM-specific molecular features, its intrinsic properties, and microenvironmental regulatory networks were considered to potentially provide new breakthroughs for overcoming treatment resistance in GBM. Methods We analyzed single-cell RNA sequencing (scRNA-seq) data processed with the Seurat package to accurately identify cell types. Spatial transcriptomics integrated Multimodal Intersection Analysis, TransferData, and Robust Cell Type Decomposition techniques to characterize the spatial distribution patterns of key cell subtypes. CellChat was employed to assess intercellular communication networks. Furthermore, in vitro experiments confirmed the main regulatory role of YEATS4 (key transcription factor of C2 PCLAF + subtype) in GBM malignant progression. Results Through scRNA-seq, we identified the C2 PCLAF + subtype in GBM and analyzed its molecular characteristics and functional role in tumor progression. This subtype exhibited a unique malignant phenotype, marked by significant proliferative activity, characteristic metabolic reprogramming, and dysregulated c...