Frontiers in Oncology (Jul 2021)
Single-Cell Transcriptomics Reveals the Complexity of the Tumor Microenvironment of Treatment-Naive Osteosarcoma
- Yun Liu,
- Wenyu Feng,
- Yan Dai,
- Yan Dai,
- Yan Dai,
- Mengying Bao,
- Mengying Bao,
- Mengying Bao,
- Zhenchao Yuan,
- Mingwei He,
- Zhaojie Qin,
- Shijie Liao,
- Juliang He,
- Qian Huang,
- Zhenyuan Yu,
- Zhenyuan Yu,
- Zhenyuan Yu,
- Yanyu Zeng,
- Yanyu Zeng,
- Yanyu Zeng,
- Binqian Guo,
- Binqian Guo,
- Binqian Guo,
- Rong Huang,
- Rong Huang,
- Rong Huang,
- Rirong Yang,
- Rirong Yang,
- Rirong Yang,
- Yonghua Jiang,
- Yonghua Jiang,
- Yonghua Jiang,
- Jinling Liao,
- Jinling Liao,
- Jinling Liao,
- Zengming Xiao,
- Xinli Zhan,
- Chengsen Lin,
- Jiake Xu,
- Yu Ye,
- Yu Ye,
- Yu Ye,
- Jie Ma,
- Qingjun Wei,
- Qingjun Wei,
- Zengnan Mo,
- Zengnan Mo,
- Zengnan Mo
Affiliations
- Yun Liu
- Department of Spinal Bone Disease, First Affiliated Hospital of Guangxi Medical University, Nanning, China
- Wenyu Feng
- Department of Trauma Orthopedic and Hand Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, China
- Yan Dai
- Center for Genomic and Personalized Medicine, School of Preclinical Medicine, Guangxi Medical University, Nanning, China
- Yan Dai
- Guangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Key Laboratory of Colleges and Universities, Nanning, China
- Yan Dai
- Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, China
- Mengying Bao
- Center for Genomic and Personalized Medicine, School of Preclinical Medicine, Guangxi Medical University, Nanning, China
- Mengying Bao
- Guangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Key Laboratory of Colleges and Universities, Nanning, China
- Mengying Bao
- Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, China
- Zhenchao Yuan
- Department of Bone and Soft Tissue Surgery, The Affiliated Tumor Hospital, Guangxi Medical University, Nanning, China
- Mingwei He
- Department of Trauma Orthopedic and Hand Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, China
- Zhaojie Qin
- Department of Spinal Bone Disease, First Affiliated Hospital of Guangxi Medical University, Nanning, China
- Shijie Liao
- Department of Trauma Orthopedic and Hand Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, China
- Juliang He
- Department of Trauma Orthopedic and Hand Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, China
- Qian Huang
- Department of Trauma Orthopedic and Hand Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, China
- Zhenyuan Yu
- Center for Genomic and Personalized Medicine, School of Preclinical Medicine, Guangxi Medical University, Nanning, China
- Zhenyuan Yu
- Guangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Key Laboratory of Colleges and Universities, Nanning, China
- Zhenyuan Yu
- Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, China
- Yanyu Zeng
- Center for Genomic and Personalized Medicine, School of Preclinical Medicine, Guangxi Medical University, Nanning, China
- Yanyu Zeng
- Guangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Key Laboratory of Colleges and Universities, Nanning, China
- Yanyu Zeng
- Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, China
- Binqian Guo
- Center for Genomic and Personalized Medicine, School of Preclinical Medicine, Guangxi Medical University, Nanning, China
- Binqian Guo
- Guangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Key Laboratory of Colleges and Universities, Nanning, China
- Binqian Guo
- Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, China
- Rong Huang
- Center for Genomic and Personalized Medicine, School of Preclinical Medicine, Guangxi Medical University, Nanning, China
- Rong Huang
- Guangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Key Laboratory of Colleges and Universities, Nanning, China
- Rong Huang
- Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, China
- Rirong Yang
- Center for Genomic and Personalized Medicine, School of Preclinical Medicine, Guangxi Medical University, Nanning, China
- Rirong Yang
- Guangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Key Laboratory of Colleges and Universities, Nanning, China
- Rirong Yang
- Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, China
- Yonghua Jiang
- Center for Genomic and Personalized Medicine, School of Preclinical Medicine, Guangxi Medical University, Nanning, China
- Yonghua Jiang
- Guangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Key Laboratory of Colleges and Universities, Nanning, China
- Yonghua Jiang
- Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, China
- Jinling Liao
- Center for Genomic and Personalized Medicine, School of Preclinical Medicine, Guangxi Medical University, Nanning, China
- Jinling Liao
- Guangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Key Laboratory of Colleges and Universities, Nanning, China
- Jinling Liao
- Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, China
- Zengming Xiao
- Department of Spinal Bone Disease, First Affiliated Hospital of Guangxi Medical University, Nanning, China
- Xinli Zhan
- Department of Spinal Bone Disease, First Affiliated Hospital of Guangxi Medical University, Nanning, China
- Chengsen Lin
- Department of Trauma Orthopedic and Hand Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, China
- Jiake Xu
- School of Biomedical Sciences, The University of Western Australia, Perth, WA, Australia
- Yu Ye
- Center for Genomic and Personalized Medicine, School of Preclinical Medicine, Guangxi Medical University, Nanning, China
- Yu Ye
- Guangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Key Laboratory of Colleges and Universities, Nanning, China
- Yu Ye
- Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, China
- Jie Ma
- Department of Medical Oncology, First Affiliated Hospital of Guangxi Medical University, Nanning, China
- Qingjun Wei
- Department of Spinal Bone Disease, First Affiliated Hospital of Guangxi Medical University, Nanning, China
- Qingjun Wei
- Guangxi Key Laboratory of Regenerative Medicine, Research Centre for Regenerative Medicine, Guangxi Medical University, Nanning, China
- Zengnan Mo
- Center for Genomic and Personalized Medicine, School of Preclinical Medicine, Guangxi Medical University, Nanning, China
- Zengnan Mo
- Guangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Key Laboratory of Colleges and Universities, Nanning, China
- Zengnan Mo
- Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, China
- DOI
- https://doi.org/10.3389/fonc.2021.709210
- Journal volume & issue
-
Vol. 11
Abstract
Osteosarcoma (OS), which occurs most commonly in adolescents, is associated with a high degree of malignancy and poor prognosis. In order to develop an accurate treatment for OS, a deeper understanding of its complex tumor microenvironment (TME) is required. In the present study, tissues were isolated from six patients with OS, and then subjected to single-cell RNA sequencing (scRNA-seq) using a 10× Genomics platform. Multiplex immunofluorescence staining was subsequently used to validate the subsets identified by scRNA-seq. ScRNA-seq of six patients with OS was performed prior to neoadjuvant chemotherapy, and data were obtained on 29,278 cells. A total of nine major cell types were identified, and the single-cell transcriptional map of OS was subsequently revealed. Identified osteoblastic OS cells were divided into five subsets, and the subsets of those osteoblastic OS cells with significant prognostic correlation were determined using a deconvolution algorithm. Thereby, different transcription patterns in the cellular subtypes of osteoblastic OS cells were reported, and key transcription factors associated with survival prognosis were identified. Furthermore, the regulation of osteolysis by osteoblastic OS cells via receptor activator of nuclear factor kappa-B ligand was revealed. Furthermore, the role of osteoblastic OS cells in regulating angiogenesis through vascular endothelial growth factor-A was revealed. C3_TXNIP+ macrophages and C5_IFIT1+ macrophages were found to regulate regulatory T cells and participate in CD8+ T cell exhaustion, illustrating the possibility of immunotherapy that could target CD8+ T cells and macrophages. Our findings here show that the role of C1_osteoblastic OS cells in OS is to promote osteolysis and angiogenesis, and this is associated with survival prognosis. In addition, T cell depletion is an important feature of OS. More importantly, the present study provided a valuable resource for the in-depth study of the heterogeneity of the OS TME.
Keywords
