Analysis of intercellular communication in the osteosarcoma microenvironment based on single cell sequencing data

Fangyi Chen; Jiao Liu; Ting Yang; Jianwei Sun; Xianwei He; Xinjie Fu; Shigang Qiao; Jianzhong An; Jiao Yang

doi:10.1016/j.jbo.2023.100493

Analysis of intercellular communication in the osteosarcoma microenvironment based on single cell sequencing data

J Bone Oncol. 2023 Jul 11:41:100493. doi: 10.1016/j.jbo.2023.100493. eCollection 2023 Aug.

Authors

Fangyi Chen¹, Jiao Liu², Ting Yang³, Jianwei Sun¹, Xianwei He¹, Xinjie Fu¹, Shigang Qiao⁴, Jianzhong An⁴, Jiao Yang⁴

Affiliations

¹ Department of Orthopedics, Jinshan Hospital, Fudan University, Shanghai, China.
² Department of Clinical Nutrition, Suzhou Municipal Hospital, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu, China.
³ School of Pharmacy, Yancheng Teachers University, Yancheng, Jiangsu, China.
⁴ Institute of Clinical Medicine Research, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University, Suzhou, Jiangsu, China.

Abstract

Osteosarcoma (OS) is the most common primary bone cancer in children and young adults, patient survival rates have not improved in recent decades. To further understand the interrelationship between different cell types in the tumor microenvironment of osteosarcoma, we comprehensively analyzed single-cell sequencing data from six patients with untreated osteosarcoma. Nine major cell types were identified from a total of 46,046 cells based on unbiased clustering of gene expression profiles and canonical markers. Osteosarcoma from different patients display heterogeneity in cellular composition. Myeloid cells were the most commonly represented cell type, followed by osteoblastic and TILs. Copy number variation (CNV) results identified amplifications and deletions in malignant osteoblastic cells and fibroblasts. Trajectory analysis based on RNA velocity showed that osteoclasts in the OS microenvironment could be differentiated from myeloid cells. Furthermore, we explored the intercellular communications in OS microenvironment and identified multiple ligand-receptor pairs between myeloid cells, osteoblastic cells and their cells, including 21 ligand-receptor pair genes that significantly associated with survival outcomes. Importantly, we found chemotherapy may have an effect on cellular communication in the OS microenvironment by analyzing single-cell sequencing data from seven primary osteosarcoma patients who received chemotherapy. We believe these observations will improve our understanding of potential mechanisms of microenvironment contributions to OS progression and help identify potential targets for new treatment development in the future.

Keywords: Intercellular communication; Microenvironment; Osteosarcoma; Single-cell sequencing.