Decoding heterogeneous and coordinated tissue architecture in glioblastoma using spatial transcriptomics
Xuejiao Lv,
Bo Wang,
Kunlun Liu,
Mulin Jun Li,
Xianfu Yi,
Xudong Wu
Affiliations
Xuejiao Lv
State Key Laboratory of Experimental Hematology, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Department of Cell Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China; Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin 300070, China
Bo Wang
Department of Neurosurgery, Clinical College of Neurology, Neurosurgery and Neurorehabilitation, Tianjin Medical University, Tianjin Huanhu Hospital, Tianjin Key Laboratory of Cerebral Vascular and Neurodegenerative Diseases, Tianjin Neurosurgical Institute, No. 6 Jizhao Road, Tianjin 300350, China
Kunlun Liu
Department of Bioinformatics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China
Mulin Jun Li
Department of Bioinformatics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China
Xianfu Yi
Department of Bioinformatics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China; Corresponding author
Xudong Wu
State Key Laboratory of Experimental Hematology, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Department of Cell Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China; Tianjin Key Laboratory of Spine and Spinal Cord, Tianjin Medical University General Hospital, Tianjin, China; Corresponding author
Summary: Glioblastoma multiforme (GBM) is one of the most lethal brain tumors, characterized by profound heterogeneity. While single-cell transcriptomic studies have revealed extensive intra-tumor heterogeneity, shed light on intra-tumor diversity, spatial intricacies remain largely unexplored. Leveraging clinical GBM specimens, this study employs spatial transcriptomics technology to delve into gene expression heterogeneity. Our investigation unveils a significant enrichment of tissue stem cell signature in regions bordering necrosis and the peritumoral area, positively correlated with the mesenchymal subtype signature. Moreover, upregulated genes in these regions are linked with extracellular matrix (ECM)-receptor interaction, proteoglycans, as well as vascular endothelial growth factor (VEGF) and angiopoietin-Tie (ANGPT) signaling pathways. In contrast, signatures related to glycogen metabolism and oxidative phosphorylation show no relevance to pathological zoning, whereas creatine metabolism signature is notably exclusive to vascular-enriched areas. These spatial profiles not only offer valuable references but also pave the way for future in-depth functional and mechanistic investigations into GBM progression.
