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A Morphometric and Cellular Analysis Method for the Murine Mandibular Condyle
Published on: January 11, 2018
Single-Cell Atlas of Human Temporomandibular Joint Condyle Identifies MXD4 as a Regulator of Chondrogenesis
Liang Wang1, Yiyi Chen2, Yuxin Zhang3
1Department of Stomatology, Affiliated Hospital of Nantong University, Institute of Special Environmental Medicine, Nantong University, Nantong, China.
Introduction And Aims:
The temporomandibular joint condyle (TMJC) is essential for mandibular and temporomandibular joint (TMJ) development. However, its cellular and molecular dynamics during human embryogenesis remain poorly understood.
Methods:
We constructed a single-cell transcriptomic atlas of the human TMJC spanning five embryonic stages from 12 to 25 gestational weeks (GW12-25). Single-cell RNA sequencing was performed to identify cell types, and Monocle 3 and SCENIC analyses were used to infer developmental trajectories and identify key transcriptional regulators. Candidate regulators were functionally validated using zebrafish models.
Results:
Single-cell RNA sequencing identified 20 major cell types within the TMJC. Immune cells were sparse at GW19 but expanded markedly by GW22. Trajectory analysis revealed a differentiation pathway from mesenchymal stem cells to chondrocytes. SCENIC analysis highlighted multiple transcription factors regulating distinct cell populations, among which MXD4 was identified for the first time as a candidate transcriptional regulator of cartilage development. Functional studies showed that mxd4 knockout in zebrafish led to craniofacial developmental abnormalities.
Conclusion:
This single-cell atlas provides a comprehensive resource for understanding the cellular and molecular mechanisms underlying TMJC development. MXD4 is identified as a candidate regulator in condylar morphogenesis.
Clinical Relevance:
Preliminary investigation of the potential regulatory role of MXD4 in condylar cartilage formation may provide a theoretical basis for diagnostic, therapeutic, and translational studies of craniofacial malformations associated with condylar hypoplasia.

