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Updated: Oct 12, 2025
Characterization of Immune Cell-derived Extracellular Vesicles and Studying Functional Impact on Cell Environment
Published on: June 2, 2020
Interrogation of the microenvironmental landscape in spinal ependymomas reveals dual functions of tumor-associated
Qianqian Zhang1,2, Sijin Cheng1, Yongzhi Wang3,4
1State Key Laboratory of Brain and Cognitive Science, CAS Center for Excellence in Brain Science and Intelligence Technology, Institute of Brain-Intelligence Technology (Shanghai), Bioland Laboratory (Guangzhou), Institute of Biophysics, Chinese Academy of Sciences, 100101, Beijing, China.
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.
Insights
Spinal ependymomas involve diverse tumor-associated macrophage (TAM) subsets influencing tumor growth and immune response. Understanding these TAMs offers new avenues for targeted immunotherapies against spinal cord tumors.
Area of Science:
- Neuro-oncology
- Immunology
- Single-cell genomics
Background:
- Spinal ependymomas are common adult spinal cord tumors.
- Intratumoral cellular heterogeneity and microglial roles in spinal ependymomas remain understudied.
Purpose of the Study:
- To dissect the microenvironmental landscape of spinal ependymomas using single-cell RNA-sequencing.
- To investigate the involvement and functional phenotypes of spinal microglia and tumor-associated macrophages (TAMs) in tumor progression.
Main Methods:
- Single-cell RNA-sequencing (scRNA-seq) analysis of three spinal ependymoma subtypes.
- Single-cell ATAC-sequencing (scATAC-seq) data analysis.
- Cell-cell interaction assessment.
Main Results:
- Identified distinct tumor-associated macrophage (TAM) subsets: CCL2+ TAMs involved in immune response and apoptosis, and CD44+ TAMs associated with tumor angiogenesis.
- Revealed roles of TEAD1 and EGR3 in regulating TAM functional diversity.
- Characterized diverse features of malignant cells and TAMs correlating with varying malignant degrees.
- Demonstrated that stromal cells mediate TAM diversity via extracellular factors.
Conclusions:
- Spinal ependymomas exhibit complex microenvironments with diverse TAM subsets playing dual roles in tumor progression.
- Findings provide valuable insights for developing TAM-targeting immunotherapies for spinal cord tumors.
