Single-Cell RNA Sequencing Study on Two Synovial Derived Tumors in the Temporomandibular Joint

To investigate the cellular composition and differentiation trajectory of synovial chondromatosis (SC) and diffuse tenosynovial giant cell tumor (D-TSGCT) in the temporomandibular joint (TMJ).

Single-cell RNA sequencing was applied to analyze the cellular composition, differentiation trajectory, and intercellular communication of SC and D-TSGCT. Cell culture and morphological experiments were applied to validate the chondrogenic differentiation potential of fibroblast-like synoviocytes (FLS) in the initial stage of SC and to explore the expression and regulation of differential genes during chondrogenic differentiation.

SC was mainly composed of FLS and chondrocytes, while D-TSGCT had a relatively complex cellular composition. Genetically, chondrogenesis-related genes such as COMP and SMAD2 were upregulated in the early stage of SC. TGFβ pathway and collagen catabolic process were subsequently activated, ultimately leading to cartilage formation. CSF1 and CD68 were overexpressed at the forming stage of D-TSGCT, and the macrophage pathway was enriched in the later phase. Based on experimental verification, COMP could induce chondrogenic differentiation of FLS by activating TGFβ/SMAD signal pathways in vitro.

FLS are the common starting point of synovial-derived tumors, but differentiate toward different endpoints in the SC and D-TSGCT. COMP/TGFβ/SMAD signaling pathways can promote chondrogenic differentiation of synovium in SC.