Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA, 90033, USA.
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Chengdu, Sichuan, 610041, China.
Nat Commun. 2022 Aug 16;13(1):4803. doi: 10.1038/s41467-022-32490-y.
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在颅面发育和功能方面的进化创新，但调控迁移后颅神经嵴细胞命运决定的机制在很大程度上仍不清楚。我们使用小鼠磨牙作为模型，通过单细胞转录组谱分析来探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全景，并在颅神经嵴细胞衍生的牙齿谱系多样化过程中定义了特定的细胞区域，发现每个区域对不同的磨牙间充质组织都有特定的贡献。此外，IGF 信号介导的细胞-细胞相互作用突出了牙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特定于细胞类型的基因调控网络，并表明 Foxp4 对于牙周韧带的分化是不可或缺的。我们的单细胞图谱为颅神经嵴细胞衍生的成牙源性群体的细胞命运多样化过程提供了全面的机制见解。
