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

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  • Qianqian Zhang

    (Institute of Brain-Intelligence Technology (Shanghai), Bioland Laboratory (Guangzhou), Institute of Biophysics, Chinese Academy of Sciences
    University of 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
    China National Clinical Research Center for Neurological Diseases)

  • 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
    University of 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
    University of Chinese Academy of Sciences)

  • Youqiao Chen

    (IDG/McGovern Institute for Brain Research, Beijing Normal University)

  • Yaowu Zhang

    (Beijing Tiantan Hospital, Capital Medical University
    China National Clinical Research Center for Neurological Diseases)

  • Ren Cao

    (Beijing Tiantan Hospital, Capital Medical University
    China National Clinical Research Center for Neurological Diseases)

  • Min Li

    (Institute of Brain-Intelligence Technology (Shanghai), Bioland Laboratory (Guangzhou), Institute of Biophysics, Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Weihao Liu

    (Beijing Tiantan Hospital, Capital Medical University
    China National Clinical Research Center for Neurological Diseases)

  • Bo Wang

    (Beijing Tiantan Hospital, Capital Medical University
    China National Clinical Research Center for Neurological Diseases)

  • Qian Wu

    (IDG/McGovern Institute for Brain Research, Beijing Normal University
    Chinese Institute for Brain Research)

  • Wenqing Jia

    (Beijing Tiantan Hospital, Capital Medical University
    China National Clinical Research Center for Neurological Diseases)

  • Xiaoqun Wang

    (Institute of Brain-Intelligence Technology (Shanghai), Bioland Laboratory (Guangzhou), Institute of Biophysics, Chinese Academy of Sciences
    University of Chinese Academy of Sciences
    Chinese Institute for Brain Research
    Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University & Capital Medical University)

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.

Suggested Citation

  • 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 , 2021. "Interrogation of the microenvironmental landscape in spinal ependymomas reveals dual functions of tumor-associated macrophages," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27018-9
    DOI: 10.1038/s41467-021-27018-9
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    1. Rachael G. Aubin & Emma C. Troisi & Javier Montelongo & Adam N. Alghalith & Maclean P. Nasrallah & Mariarita Santi & Pablo G. Camara, 2022. "Pro-inflammatory cytokines mediate the epithelial-to-mesenchymal-like transition of pediatric posterior fossa ependymoma," Nature Communications, Nature, vol. 13(1), pages 1-14, December.

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