1. Interrogation of the microenvironmental landscape in spinal ependymomas reveals dual functions of tumor-associated macrophages
- Author
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Min Li, Wei-Hao Liu, Qiang Ma, Yuxin Ge, Bo Wang, Yong-Zhi Wang, Yao-Wu Zhang, Ren Cao, Zengqi Wen, Wenqing Jia, Yufeng Lu, Sijin Cheng, Qianqian Zhang, Youqiao Chen, Xiaoqun Wang, Mengdi Wang, and Qian Wu
- Subjects
Ependymoma ,Stromal cell ,medicine.medical_treatment ,Science ,General Physics and Astronomy ,Apoptosis ,Cell Communication ,Article ,General Biochemistry, Genetics and Molecular Biology ,Genetic Heterogeneity ,stomatognathic system ,Tumor-Associated Macrophages ,Tumor Microenvironment ,medicine ,Humans ,Macrophage ,Spinal Cord Neoplasms ,skin and connective tissue diseases ,Multidisciplinary ,Neovascularization, Pathologic ,biology ,Microglia ,CD44 ,General Chemistry ,Immunotherapy ,medicine.disease ,Phenotype ,CNS cancer ,medicine.anatomical_structure ,Tumor progression ,biology.protein ,Cancer research ,Single-Cell Analysis ,Stromal Cells ,Transcriptome ,Cancer in the nervous system ,hormones, hormone substitutes, and hormone antagonists - Abstract
Spinal ependymomas are the most common spinal cord tumors in adults, but their intratumoral cellular heterogeneity has been less studied, and how spinal microglia are involved in tumor progression is still unknown. Here, our single-cell RNA-sequencing analyses of three spinal ependymoma subtypes dissect the microenvironmental landscape of spinal ependymomas and reveal tumor-associated macrophage (TAM) subsets with distinct functional phenotypes. CCL2+ TAMs are related to the immune response and exhibit a high capacity for apoptosis, while CD44+ TAMs are associated with tumor angiogenesis. By combining these results with those of single-cell ATAC-sequencing data analysis, we reveal that TEAD1 and EGR3 play roles in regulating the functional diversity of TAMs. We further identify diverse characteristics of both malignant cells and TAMs that might underlie the different malignant degrees of each subtype. Finally, assessment of cell-cell interactions reveal that stromal cells act as extracellular factors that mediate TAM diversity. Overall, our results reveal dual functions of TAMs in tumor progression, providing valuable insights for TAM-targeting immunotherapy., The intratumoural heterogeneity of spinal ependymomas and the role of microglia in tumour progression remain underexplored. Here, the authors perform single-cell RNA- and ATAC-sequencing data analysis of three subtypes and reveal tumour-associated macrophage subsets with distinct functional phenotypes.
- Published
- 2021