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

Abstract

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.

Single-cell RNA sequencing reveals differential expression of EGFL7 and VEGF in giant-cell tumor of bone and osteosarcoma

“…We have previously shown that EGFL7 is expressed in GCTB tumor tissues. 1 Additional studies detected and localized expression of EGFL7 in OS tissues. 31 VEGF - A was identified in both OS and GCTB tissues.…”

“…To define the heterogeneity of GCTB and OS tumor cells at the transcriptional level, we performed bioinformatic analysis using results obtained from our previously published studies. 1,30 The mRNA expression data used in this study were downloaded from the NCBI Gene Expression Omnibus database. We refer to each dataset by the first author’s last name and cancer type.…”

CD137 Regulates Bone Loss via the p53 Wnt/β-Catenin Signaling Pathways in Aged Mice

“…CCNA2 also has important roles in initiating osteogenesis, adipogenesis, and chondrogenesis (34). In particular, CD137 not only has a high degree score in the PPI network but also are closely related to osteoclasts based on Feng's study (35). CD137L and CD137 expressed on BMSCs promote the osteogenic differentiation through p53 Wnt/b-catenin signaling.What is more, we speculated that CD137 expression was up-regulated in BMSCs isolated of aged mice, affecting the osteogenic differentiation of BMSCs by the p53 Wnt/b-catenin pathway.…”

Interactions in CSF1-driven Tenosynovial Giant Cell Tumors

“…Third, while the giant cells in TGCT and GCTB appear quite large in histologic images, the giant cells in GCTB have been measured as having size range of 10-300um (31). Finally, other groups were also able to study giant cells using single cell sequencing, such as the single cell study of GCTB (32, 33). The presence of giant cells in the scRNA data allowed to compare them to those found in Giant Cell Tumor of Bone (GCTB) that has several similarities with TGCT.…”