TY - JOUR T1 - Single-cell RNA-seq reveals identity and heterogeneity of malignant osteoblast cells and TME in osteosarcoma JF - bioRxiv DO - 10.1101/2020.04.16.044370 SP - 2020.04.16.044370 AU - Yan Zhou AU - Dong Yang AU - Qing-Cheng Yang AU - Xiao-Bin Lv AU - Wen-Tao Huang AU - Zhenhua Zhou AU - Ya-Ling Wang AU - Zhichang Zhang AU - Ting Yuan AU - Xiaomin Ding AU - Li-Na Tang AU - Jian-Jun Zhang AU - Jun-Yi Yin AU - Yu-Jing Huang AU - Wen-Xi Yu AU - Yong-Gang Wang AU - Chen-Liang Zhou AU - Yang Su AU - Ai-Na He AU - Yuan-Jue Sun AU - Zan Shen AU - Bin-Zhi Qian AU - Peizhan Chen AU - Xinghua Pan AU - Yang Yao AU - Hai-Yan Hu Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/04/16/2020.04.16.044370.abstract N2 - Osteosarcoma (OS) has high heterogeneity and poor prognosis. In order to explore the molecular mechanism of OS and the tumor micro-environment (TME) on OS, we employed single-cell RNA-sequencing (scRNA-seq) on 110,745 individual cells from OS primary lesion, recurrent focal and metastatic tissues. We identified 5 main malignant subpopulations of OS cells, 3 clusters of osteoclast(OC) and 2 types of cancer-associated fibroblasts (CAFs). Further we found that the progenitor OC and, antigen presenting CAF (apCAF) were lower in lung metastatic and recurrent tumor tissues than in primary tumor tissue. M2-like macrophages were predominant in the TME myeloid cells. Inactivation state of tumor-infiltrating T cells, mainly the CD4-/CD8-T and Treg cells, existed in lung metastatic tissues. T-cell immunoreceptor with Ig and ITIM domains (TIGIT) expressed in 11 samples. We then blocked TIGIT which significantly enhancd the cytotoxic effects of primary T cells on OS cell lines. Our report represents the first use of scRNA-seq for the transcriptomic profiling of OS cells. Thus, the findings in this study will serve as a valuable resource for deciphering the intra-tumoral heterogeneity in OS and provide potential therapeutic strategies for OS in clinic.Competing Interest StatementThe authors have declared no competing interest. ER -