Spatial Transcriptome Assays Reveals Gliomas Heterogeneity

Background: Glioma is a kind of highly heterogeneous central nervous system malignancy and controlled by various molecular processes such as neoplastic transformation, dysregulation of the cell cycle, and angiogenesis. Among these biomolecular events, the existence of inflammation and stress pathways in the development and driving factors of glioma heterogeneity has been reported. However, mechanisms of glioma heterogeneous under stress response remain unclear, especially from a spatial aspect. Methods: This study combined single-cell and spatially resolved transcriptomics and revealed that oxidative stress response genes play a vital role in oligodendrocyte precursor cells from two different types of gliomas: high- and low-grade (HG and LG). Results: In HG, stress triggers metabolic pattern changes from oxidative phosphorylation to glycolysis to avoid apoptosis, along with epithelial-to-mesenchymal transition and increased expression of genes of stress response. Scenic analysis indicated that oxidative stress induced the activation of AP1 in HG, thus enhancing the tumor survival and proliferation process. Conclusion: When all of these factors are considered together, we provide a unique perspective on how oxidative stress response occurs in different grades of gliomas, which would deepen our understanding of evolution and heterogeneity in gliomas. Our primary glioma samples were obtained from untreated patients and analyzed using single-cell spatial transcriptomics profiling