Single-Cell RNA Sequencing Reveals the Migration of Osteoclasts in Giant Cell Tumor of Bone

Frontiers in Oncology

Juliang He¹  Jie Ma²  Huijiang Liu³  Yun Liu⁴  Zhaojie Qin⁴  Shijie Liao⁵  Qian Huang⁵  Wenyu Feng⁵  Tianyu Xie⁵  Chengsen Lin⁵  Qingjun Wei⁵  Xiaohong Jiang⁶  Mingwei He⁷  Jiake Xu⁸ 

[1] Department of Bone and Soft Tissue Surgery, Guangxi Medical University Cancer Hospital, Nanning, China;Department of Medical Oncology, First Affiliated Hospital of Guangxi Medical University, Nanning, China;Department of Orthopedics, The First People’s Hospital of Nanning, Nanning, China;Department of Spinal Bone Disease, First Affiliated Hospital of Guangxi Medical University, Nanning, China;Department of Trauma Orthopedic and Hand Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, China;Department of Orthopedic, Affiliated Minzu Hospital of Guangxi Medical University, Nanning, China;Guangxi Collaborative Innovation Center for Biomedicine, Guangxi Medical University, Nanning, China;School of Biomedical Sciences, The University of Western Australia, Perth, WA, Australia;

关键词: single cell RNA sequence;    giant cell tumor of bone (GCTB);    osteolysis;    osteoclast;    migration;   

DOI  :  10.3389/fonc.2021.715552

来源: DOAJ

【 摘 要 】

Giant cell tumor of bone (GCTB) is benign tumor that can cause significant osteolysis and bone destruction at the epiphysis of long bones. Osteoclasts are thought to be highly associated with osteolysis in GCTB. However, the migration of osteoclasts in GCTB remains unclear. A deeper understanding of the complex tumor microenvironment is required in order to delineate the migration of osteoclasts in GCTB. In this study, samples were isolated from one patient diagnosed with GCTB. Single-cell RNA sequencing (scRNA-seq) was used to detect the heterogeneity of GCTB. Multiplex immunofluorescence staining was used to evaluate the cell subtypes identified by scRNA-seq. A total of 8,033 cells were obtained from one patient diagnosed with GCTB, which were divided into eight major cell types as depicted by a single-cell transcriptional map. The osteoclasts were divided into three subsets, and their differentiation trajectory and migration status were further analyzed. Osteoclast migration may be regulated via a series of genes associated with cell migration. Furthermore, four signaling pathways (RANKL, PARs, CD137 and SMEA3 signaling pathway) were found to be highly associated with osteoclast migration. This comprehensive single-cell transcriptome analysis of GCTB identified a series of genes associated with cell migration as well as four major signaling pathways that were highly related to the migration of osteoclasts in GCTB. Our findings broaden the understanding of GCTB bionetworks and provides a theoretical basis for anti-osteolysis therapy against GCTB in the future.

【 授权许可】

Unknown