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Interrogation of the microenvironmental landscape in spinal ependymomas reveals dual functions of tumor-associated macrophages
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Interrogation of the microenvironmental landscape in spinal ependymomas reveals dual functions of tumor-associated macrophages
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Journal Article
Interrogation of the microenvironmental landscape in spinal ependymomas reveals dual functions of tumor-associated macrophages
2021
Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 14/19
/ 38/91
/ Humanities and Social Sciences
/ Humans
/ Monocyte chemoattractant protein 1
/ Neovascularization, Pathologic - pathology
/ Science
/ Spinal Cord Neoplasms - genetics
/ Spinal Cord Neoplasms - pathology
/ Tumor-Associated Macrophages - metabolism
/ Tumor-Associated Macrophages - pathology
/ Tumors
