A single-cell transcriptomic atlas identifies hierarchical skeletal progenitors and zonal patterning in mouse
Ikue Tosa1, Wakana Kitagawa2, Benjamin Kheyfets2
1Columbia University Irving Medical Center, College of Dental Medicine, Cartilage Biology and Regenerative Medicine Laboratory, New York, NY, USA; Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Department of Oral Microbiology, Okayama, Okayama, Japan.
None:
Skeletal and synovial joint development involves distinct skeletal stem/progenitor populations. However, in neural crest-derived temporomandibular joint (TMJ), skeletal stem/progenitor lineage dynamics and ossification programs remain poorly defined. Here, we performed single-cell RNA sequencing (scRNA-seq) on mouse mandibular cartilage at embryonic day 16.5 (E16.5), postnatal day 0 (P0), and 13 weeks to construct a high-resolution atlas of skeletal stem/progenitor populations. At embryonic and postnatal stages, the outer perichondrium contained Lgr5+Pthlh+ cells expressing Dlx5, consistent with an intramembranous ossification-associated program. In contrast, a previously uncharacterized Crabp1+ subpopulation within the inner perichondrium expressed Nrg1, Lsamp, Tac1, and Igfbp5, consistent with an early chondrogenic-associated transcriptional state. These results suggest spatially distinct ossification-associated programs and reveal the transcriptional regulation underlying TMJ development. Our findings provide a model for understanding neural crest-derived TMJ skeletal stem/progenitor cell regulation and may inform future studies of TMJ cartilage biology and regeneration strategies within this specialized tissue.
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