The cell developmental atlas of human embryonic temporomandibular joint

Abstract Background: The temporomandibular joint (TMJ) is a complex joint consisting of the mandibular condyle, temporal articular surface, and articular disc. The functions of mastication, swallowing and articulation are accomplished by the movements of the TMJ. To date, the TMJ has been studied more extensively, but the study of the TMJ is limited by the type of TMJ cells, their differentiation, and their interrelationship during growth and development is unclear. The aim of this study is to establish a molecular cellular developmental atlas of the human TMJ by single-cell RNA sequencing, which will contribute to understanding and solving. Results: We performed a comprehensive transcriptome analysis of TMJ tissue from 3- and 4-month-old human embryos using single-cell RNA sequencing. A total of 15,624 cells were captured and the gene expression profiles of 15 cell populations in human TMJ were determined, including 14 known cell types and a previously unknown cell type named "transition state cells (TSCs)". Immunofluorescence assays confirmed that TSCs are not the same cell cluster as mesenchymal stem cells (MSCs). Pseudotime trajectory and RNA velocity analysis showed that MSCs transformed into TSCs, and TSCs further differentiated into tenocytes, hypertrophic chondrocytes and osteoblasts. In addition, chondrocytes were detected only in 4-month-old human embryonic TMJ. Conclusions: Our study provides an atlas of the earlier cellular development of human embryonic TMJ tissue, which will contribute to a deeper understanding of the pathophysiology of TMJ tissue during repair and ultimately help to solve clinical problems.