Cranial neural crest cells are an evolutionary innovation of vertebrates for craniofacial development and function, yet the mechanisms that govern the cell fate decisions of postmigratory cranial neural crest cells remain largely unknown. Using the mouse molar as a model, we perform single-cell transcriptome profiling to interrogate the cell fate diversification of postmigratory cranial neural crest cells. We reveal the landscape of transcriptional heterogeneity and define the specific cellular domains during the progression of cranial neural crest cell-derived dental lineage diversification, and find that each domain makes a specific contribution to distinct molar mesenchymal tissues. Furthermore, IGF signaling-mediated cell-cell interaction between the cellular domains highlights the pivotal role of autonomous regulation of the dental mesenchyme. Importantly, we reveal cell-type-specific gene regulatory networks in the dental mesenchyme and show that Foxp4 is indispensable for the differentiation of periodontal ligament. Our single-cell atlas provides comprehensive mechanistic insight into the cell fate diversification process of the cranial neural crest cell-derived odontogenic populations.

颅神经嵴细胞是脊椎动物颅面发育和功能的进化创新，但控制迁移后颅神经嵴细胞的细胞命运决定的机制在很大程度上仍然未知。我们使用小鼠磨牙作为模型，进行单细胞转录组分析，以研究迁移后颅神经嵴细胞的细胞命运多样化。我们揭示了转录异质性的景观，并定义了颅神经嵴细胞衍生的牙科谱系多样化进程中的特定细胞域，并发现每个域对不同的臼齿间充质组织都有特定的贡献。此外，IGF 信号介导的细胞结构域之间的细胞间相互作用突出了牙科间充质自主调节的关键作用。重要的是，我们揭示了牙间充质中细胞类型特异性的基因调控网络，并表明 Foxp4 对于牙周膜的分化是必不可少的。我们的单细胞图谱提供了对颅神经嵴细胞衍生的牙源性群体的细胞命运多样化过程的全面机制洞察。