AUTHOR=Wu Rong , Dou Xiaojie , Li Haidong , Sun Zhenguo , Li Heng , Shen Yuxin , Weng Wei , Min Jikang 

TITLE=Identification of Cell Subpopulations and Interactive Signaling Pathways From a Single-Cell RNA Sequencing Dataset in Osteosarcoma: A Comprehensive Bioinformatics Analysis

JOURNAL=Frontiers in Oncology

VOLUME=Volume 12 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.853979

DOI=10.3389/fonc.2022.853979

ISSN=2234-943X

ABSTRACT=Osteosarcoma is a type of highly aggressive bone tumor arising from primitive cells of mesenchymal origin in the adults, and is associated with high rate of tumor relapse. However, there is an urgent need to clarify the molecular mechanisms underlying osteosarcoma development. The present study performed the integrated bioinformatics analysis in the single-cell RNA sequencing dataset and explored the potential interactive signalling pathways associated with osteosarcoma development. Single-cell transcriptomic analysis of osteosarcoma tissues was performed by using Seurat R package; the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of differentially expressed genes was performed by clusterProfiler R package; the cell-cell interaction analysis performed by using Cellphone DB package. Our results showed that 11 clustered cell types were identified across 11 osteosarcoma tissues, with cell types including “osteoblastic”, “myeloid”, “osteoblastic_proli”, “osteoclast” and “tumor-infiltrating lymphocytes (TIL)” as main types. The DEGs between different cell types from primary, metastatic and recurrent osteosarcoma were mainly enriched in the GO terms including “negative regulation of hydrolase activity”, “regulation of peptidase activity”, “regulation of binding”, “negative regulation of proteolysis”, “negative regulation of peptidase activity” and in the KEGG pathways including “transcriptional misregulation in cancer”, “cellular senescence”, “apoptosis”, “FoxO signaling pathway”, “cell cycle”, “NF-kappB signaling pathway”, “p53 signaling pathway”, “pentose phosphate pathway” and “protein export”. For the cell-cell communication network analysis, the different interaction profiles between cell types were detected among the primary, metastatic and recurrent osteosarcoma. Further exploration of KEGG pathway revealed that these liangs/receptors interactions may be associated with the NF-B signaling pathway and its interacted mediators. In conclusion, the present study for the first explored the scRNA-seq dataset in osteosarcoma, and our results revealed the 11 clustered cell types and demonstrated the novel cell-cell interactions among different cell types in primary, metastatic and recurrent osteosarcoma. NF-B singaling pathway may play a key role in regulating TME of osteosarcoma. The present study may provide new insights into understanding the molecular mechanisms of osteosarcoma pathophysiology.