Single-Cell Transcriptomics Reveals the Complexity of the Tumor Microenvironment of Treatment-Naive Osteosarcoma
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 isolat...
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| Format: | Article |
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Frontiers Media S.A.
2021-07-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.709210/full |
| _version_ | 1811225320074772480 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Yun Liu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T09:05:05Z |
| format | Article |
| id | doaj.art-8b135de44da548f89448dba121e21f40 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-12T09:05:05Z |
| publishDate | 2021-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-8b135de44da548f89448dba121e21f402022-12-22T03:39:08ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-07-011110.3389/fonc.2021.709210709210Single-Cell Transcriptomics Reveals the Complexity of the Tumor Microenvironment of Treatment-Naive OsteosarcomaYun Liu0Wenyu Feng1Yan Dai2Yan Dai3Yan Dai4Mengying Bao5Mengying Bao6Mengying Bao7Zhenchao Yuan8Mingwei He9Zhaojie Qin10Shijie Liao11Juliang He12Qian Huang13Zhenyuan Yu14Zhenyuan Yu15Zhenyuan Yu16Yanyu Zeng17Yanyu Zeng18Yanyu Zeng19Binqian Guo20Binqian Guo21Binqian Guo22Rong Huang23Rong Huang24Rong Huang25Rirong Yang26Rirong Yang27Rirong Yang28Yonghua Jiang29Yonghua Jiang30Yonghua Jiang31Jinling Liao32Jinling Liao33Jinling Liao34Zengming Xiao35Xinli Zhan36Chengsen Lin37Jiake Xu38Yu Ye39Yu Ye40Yu Ye41Jie Ma42Qingjun Wei43Qingjun Wei44Zengnan Mo45Zengnan Mo46Zengnan Mo47Department of Spinal Bone Disease, First Affiliated Hospital of Guangxi Medical University, Nanning, ChinaDepartment of Trauma Orthopedic and Hand Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, ChinaCenter for Genomic and Personalized Medicine, School of Preclinical Medicine, Guangxi Medical University, Nanning, ChinaGuangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Key Laboratory of Colleges and Universities, Nanning, ChinaGuangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, ChinaCenter for Genomic and Personalized Medicine, School of Preclinical Medicine, Guangxi Medical University, Nanning, ChinaGuangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Key Laboratory of Colleges and Universities, Nanning, ChinaGuangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, ChinaDepartment of Bone and Soft Tissue Surgery, The Affiliated Tumor Hospital, Guangxi Medical University, Nanning, ChinaDepartment of Trauma Orthopedic and Hand Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, ChinaDepartment of Spinal Bone Disease, First Affiliated Hospital of Guangxi Medical University, Nanning, ChinaDepartment of Trauma Orthopedic and Hand Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, ChinaDepartment of Trauma Orthopedic and Hand Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, ChinaDepartment of Trauma Orthopedic and Hand Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, ChinaCenter for Genomic and Personalized Medicine, School of Preclinical Medicine, Guangxi Medical University, Nanning, ChinaGuangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Key Laboratory of Colleges and Universities, Nanning, ChinaGuangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, ChinaCenter for Genomic and Personalized Medicine, School of Preclinical Medicine, Guangxi Medical University, Nanning, ChinaGuangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Key Laboratory of Colleges and Universities, Nanning, ChinaGuangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, ChinaCenter for Genomic and Personalized Medicine, School of Preclinical Medicine, Guangxi Medical University, Nanning, ChinaGuangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Key Laboratory of Colleges and Universities, Nanning, ChinaGuangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, ChinaCenter for Genomic and Personalized Medicine, School of Preclinical Medicine, Guangxi Medical University, Nanning, ChinaGuangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Key Laboratory of Colleges and Universities, Nanning, ChinaGuangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, ChinaCenter for Genomic and Personalized Medicine, School of Preclinical Medicine, Guangxi Medical University, Nanning, ChinaGuangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Key Laboratory of Colleges and Universities, Nanning, ChinaGuangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, ChinaCenter for Genomic and Personalized Medicine, School of Preclinical Medicine, Guangxi Medical University, Nanning, ChinaGuangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Key Laboratory of Colleges and Universities, Nanning, ChinaGuangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, ChinaCenter for Genomic and Personalized Medicine, School of Preclinical Medicine, Guangxi Medical University, Nanning, ChinaGuangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Key Laboratory of Colleges and Universities, Nanning, ChinaGuangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, ChinaDepartment of Spinal Bone Disease, First Affiliated Hospital of Guangxi Medical University, Nanning, ChinaDepartment of Spinal Bone Disease, First Affiliated Hospital of Guangxi Medical University, Nanning, ChinaDepartment of Trauma Orthopedic and Hand Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, ChinaSchool of Biomedical Sciences, The University of Western Australia, Perth, WA, AustraliaCenter for Genomic and Personalized Medicine, School of Preclinical Medicine, Guangxi Medical University, Nanning, ChinaGuangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Key Laboratory of Colleges and Universities, Nanning, ChinaGuangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, ChinaDepartment of Medical Oncology, First Affiliated Hospital of Guangxi Medical University, Nanning, ChinaDepartment of Spinal Bone Disease, First Affiliated Hospital of Guangxi Medical University, Nanning, ChinaGuangxi Key Laboratory of Regenerative Medicine, Research Centre for Regenerative Medicine, Guangxi Medical University, Nanning, ChinaCenter for Genomic and Personalized Medicine, School of Preclinical Medicine, Guangxi Medical University, Nanning, ChinaGuangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Key Laboratory of Colleges and Universities, Nanning, ChinaGuangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, ChinaOsteosarcoma (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.https://www.frontiersin.org/articles/10.3389/fonc.2021.709210/fullsingle-cell RNA sequencingtumor microenvironmentnaive osteosarcomaheterogeneityosteolysis |
| spellingShingle | 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 Single-Cell Transcriptomics Reveals the Complexity of the Tumor Microenvironment of Treatment-Naive Osteosarcoma Frontiers in Oncology single-cell RNA sequencing tumor microenvironment naive osteosarcoma heterogeneity osteolysis |
| title | Single-Cell Transcriptomics Reveals the Complexity of the Tumor Microenvironment of Treatment-Naive Osteosarcoma |
| title_full | Single-Cell Transcriptomics Reveals the Complexity of the Tumor Microenvironment of Treatment-Naive Osteosarcoma |
| title_fullStr | Single-Cell Transcriptomics Reveals the Complexity of the Tumor Microenvironment of Treatment-Naive Osteosarcoma |
| title_full_unstemmed | Single-Cell Transcriptomics Reveals the Complexity of the Tumor Microenvironment of Treatment-Naive Osteosarcoma |
| title_short | Single-Cell Transcriptomics Reveals the Complexity of the Tumor Microenvironment of Treatment-Naive Osteosarcoma |
| title_sort | single cell transcriptomics reveals the complexity of the tumor microenvironment of treatment naive osteosarcoma |
| topic | single-cell RNA sequencing tumor microenvironment naive osteosarcoma heterogeneity osteolysis |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.709210/full |
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