A single-cell transcriptional atlas reveals resident progenitor cell niche functions in TMJ disc development and injury

The biological characteristics of the temporomandibular joint disc involve complex cellular network in cell identity and extracellular matrix composition to modulate jaw function. The lack of a detailed characterization of the network severely limits the development of targeted therapies for temporomandibular joint-related diseases. Here we profiled single-cell transcriptomes of disc cells from mice at different postnatal stages, finding that the fibroblast population could be divided into chondrogenic and non-chondrogenic clusters. We also find that the resident mural cell population is the source of disc progenitors, characterized by ubiquitously active expression of the NOTCH3 and THY1 pathways. Lineage tracing reveals that Myh11(+) mural cells coordinate angiogenesis during disc injury but lost their progenitor characteristics and ultimately become Sfrp2(+) non-chondrogenic fibroblasts instead of Chad(+) chondrogenic fibroblasts. Overall, we reveal multiple insights into the coordinated development of disc cells and are the first to describe the resident mural cell progenitor during disc injury. The transcriptional network in TMJ disc development and injury remains poorly characterized. Here they generate a scRNA-seq atlas of mouse TMJ disc, and identify the resident progenitor population and how its transcriptional reprogramming contributes to disc repair.

Automated summary

The biological characteristics of the temporomandibular joint disc involve a complex cellular network that regulates jaw function. However, the lack of detailed understanding about this network hinders the development of targeted therapies for temporomandibular joint-related diseases. In this study, the researchers profiled the transcriptomes of disc cells from mice at different stages and found distinct fibroblast populations and a resident progenitor population that contributes to disc repair. This study provides valuable insights into the development and injury repair mechanisms of the temporomandibular joint disc.