机构：[1]Department of Neurosurgery, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China,四川省人民医院[2]Department of Medicine, Baylor College of Medicine, Houston, TX, United States,[3]Medical School, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China,[4]Center of Critical Care Medicine, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China,[5]Department of Otolaryngology, Chongqing General Hospital of the Chinese People’s Armed Police Force, Chongqing, China,[6]Department of Health Management, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China,四川省人民医院[7]The Key Laboratory for Human Disease Gene Study of Sichuan Province and Institute of Laboratory Medicine, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China,四川省人民医院[8]Department of Neuroscience, Baylor College of Medicine, Houston, TX, United States,[9]Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Academy of Medical Science and Sichuan Provincial People’s Hospital, Chengdu, China四川省人民医院
Background Glioma is a highly heterogeneous malignancy of the central nervous system. This heterogeneity is driven by various molecular processes, including neoplastic transformation, cell cycle dysregulation, and angiogenesis. Among these biomolecular events, inflammation and stress pathways in the development and driving factors of glioma heterogeneity have been reported. However, the mechanisms of glioma heterogeneity under stress response remain unclear, especially from a spatial aspect.Methods This study employed single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) to explore the impact of oxidative stress response genes in oligodendrocyte precursor cells (OPCs). Our analysis identified distinct pathways activated by oxidative stress in two different types of gliomas: high- and low- grade (HG and LG) gliomas.Results In HG gliomas, oxidative stress induced a metabolic shift from oxidative phosphorylation to glycolysis, promoting cell survival by preventing apoptosis. This metabolic reprogramming was accompanied by epithelial-to-mesenchymal transition (EMT) and an upregulation of stress response genes. Furthermore, SCENIC (Single-Cell rEgulatory Network Inference and Clustering) analysis revealed that oxidative stress activated the AP1 transcription factor in HG gliomas, thereby enhancing tumor cell survival and proliferation.Conclusion Our findings provide a novel perspective on the mechanisms of oxidative stress responses across various grades of gliomas. This insight enhances our comprehension of the evolutionary processes and heterogeneity within gliomas, potentially guiding future research and therapeutic strategies.
基金：
Natural Science Foundation of China [81802504]; Health Commission Of Sichuan Provincial, China [23LCYJ035]; Sichuan Science and Technology Program, China [2023YFS0107, 2023YFS0106]
第一作者机构：[1]Department of Neurosurgery, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China,
共同第一作者：
通讯作者：
通讯机构：[4]Center of Critical Care Medicine, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China,[6]Department of Health Management, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China,[7]The Key Laboratory for Human Disease Gene Study of Sichuan Province and Institute of Laboratory Medicine, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China,[9]Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Academy of Medical Science and Sichuan Provincial People’s Hospital, Chengdu, China
推荐引用方式(GB/T 7714)：
He Zongze,Liu Zheng,Wang Qi,et al.Single-cell and spatial transcriptome assays reveal heterogeneity in gliomas through stress responses and pathway alterations[J].FRONTIERS IN IMMUNOLOGY.2024,15:doi:10.3389/fimmu.2024.1452172.
APA：
He, Zongze,Liu, Zheng,Wang, Qi,Sima, Xingjian,Zhao, Wei...&Wang, Yi.(2024).Single-cell and spatial transcriptome assays reveal heterogeneity in gliomas through stress responses and pathway alterations.FRONTIERS IN IMMUNOLOGY,15,
MLA：
He, Zongze,et al."Single-cell and spatial transcriptome assays reveal heterogeneity in gliomas through stress responses and pathway alterations".FRONTIERS IN IMMUNOLOGY 15.(2024)
