Single-cell transcriptional atlas revealed that the resident progenitor cell niche functions in TMJ disc development and injury

ABSTRACT: The biological characteristics of the temporomandibular joint (TMJ) disc involve complex changes in cell identity and extracellular matrix (ECM) composition to modulate jaw function during postnatal growth and aging. To better understand this process, we profiled and analyzed 39111 single-cell transcriptomes of TMJ disc cells from mice at different postnatal stages. Our data showed that TMJ disc cells are composed of 9 distinct clusters that can be divided into 4 principal cell types: fibroblasts (FBs), which were the most abundant, endothelial cells (ECs), macrophages (MPhs) and mural cells (MCs). FBs were found to exhibit heterogeneity in terms of biological processes related to ECM secretion and metabolic functions. The ECs and MPhs mainly clustered together in the junction of the anterior disc band and anterior attachment, indicating the potential importance of the inflammatory response in this region in the pathological process of disc diseases. Notably, we found for the first time that resident MCs are the source of the progenitor niche in TMJ discs. The pseudotime trajectory showed that MCs have 2 lineage fates: self-renewal or multidirectional differentiation toward functional cells. In MCs, the NOTCH3 and THY1 signaling pathways were ubiquitously active at all stages, coupled with specific gene expression of Notch3 and Thy1 in MCs, indicating the critical role of these molecules in MC characteristics. As an example, THY1+ cells in TMJ discs showed markedly stronger stem cell characteristics than THY1- disc cells in vitro and ex vivo. In addition, lineage tracing in vivo showed that the Myh11-CreER+ MC lineage proliferated and migrated to coordinate angiogenesis during disc injury but gradually lost its progenitor characteristics and ultimately became a functional cell for disc repair. Overall, we reveal multiple insights into the coordinated and temporal development of TMJ disc cells at different postnatal stages and are the first to describe the resident MC progenitor cell niche during TMJ disc growth and injury.

ORGANISM(S): Mus musculus

PROVIDER: GSE218785 | GEO | 2022/12/01

REPOSITORIES: GEO