Interrogation of the microenvironmental landscape in spinal ependymomas reveals dual functions of tumor-associated macrophages

Qianqian Zhang, Sijin Cheng, Yongzhi Wang, Mengdi Wang, Yufeng Lu, Zengqi Wen, Yuxin Ge, Qiang Ma, Youqiao Chen, Yaowu Zhang, Ren Cao, Min Li, Weihao Liu, Bo Wang, Qian Wu (), Wenqing Jia () and Xiaoqun Wang ()
Additional contact information
Qianqian Zhang: Institute of Brain-Intelligence Technology (Shanghai), Bioland Laboratory (Guangzhou), Institute of Biophysics, Chinese Academy of Sciences
Sijin Cheng: Institute of Brain-Intelligence Technology (Shanghai), Bioland Laboratory (Guangzhou), Institute of Biophysics, Chinese Academy of Sciences
Yongzhi Wang: Beijing Tiantan Hospital, Capital Medical University
Mengdi Wang: Institute of Brain-Intelligence Technology (Shanghai), Bioland Laboratory (Guangzhou), Institute of Biophysics, Chinese Academy of Sciences
Yufeng Lu: Institute of Brain-Intelligence Technology (Shanghai), Bioland Laboratory (Guangzhou), Institute of Biophysics, Chinese Academy of Sciences
Zengqi Wen: Institute of Brain-Intelligence Technology (Shanghai), Bioland Laboratory (Guangzhou), Institute of Biophysics, Chinese Academy of Sciences
Yuxin Ge: IDG/McGovern Institute for Brain Research, Beijing Normal University
Qiang Ma: Institute of Brain-Intelligence Technology (Shanghai), Bioland Laboratory (Guangzhou), Institute of Biophysics, Chinese Academy of Sciences
Youqiao Chen: IDG/McGovern Institute for Brain Research, Beijing Normal University
Yaowu Zhang: Beijing Tiantan Hospital, Capital Medical University
Ren Cao: Beijing Tiantan Hospital, Capital Medical University
Min Li: Institute of Brain-Intelligence Technology (Shanghai), Bioland Laboratory (Guangzhou), Institute of Biophysics, Chinese Academy of Sciences
Weihao Liu: Beijing Tiantan Hospital, Capital Medical University
Bo Wang: Beijing Tiantan Hospital, Capital Medical University
Qian Wu: IDG/McGovern Institute for Brain Research, Beijing Normal University
Wenqing Jia: Beijing Tiantan Hospital, Capital Medical University
Xiaoqun Wang: Institute of Brain-Intelligence Technology (Shanghai), Bioland Laboratory (Guangzhou), Institute of Biophysics, Chinese Academy of Sciences

Nature Communications, 2021, vol. 12, issue 1, 1-17

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-27018-9

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