Single-cell transcriptome profiling reveals developmental trajectory and transcriptional regulatory networks of mouse maxillary prominence

During embryonic development of vertebrates, neural crest- derived mesenchymal cells within the maxillary prominences undergo precisely coordinated proliferation and differentiation to give rise to a series of craniofacial structures, such as tooth and secondary palate. However, the transcriptional regulatory networks underpinning such an intricate process have not been fully elucidated. Here we combined bulk and single-cell RNA-Seq to comprehensively characterize the transcriptome dynamics during mouse maxillary development from embryonic day (E) 10.5 to 14.5. We identified mesenchymal cell populations that represent different developmental states and inferred their developmental trajectory, demonstrating that a cell fate divergence toward the palatal versus dental mesenchyme lineage occurs at E11.5. We further identified the core transcriptional regulators associated with maxillary cell fate transitions and deduced the gene regulatory networks directed by these factors. We further demonstrated that Foxp1 regulates genes involved in skeletal and cartilage development and is required for efficient osteogenesis. Collectively, our study provides rich resources and important insights for achieving a systems level understanding of craniofacial morphogenesis and abnormality. Single cell RNA-Seq of E10.5, E11.5, E12.5, E14.5 mouse embryonic maxillary prominence tissue.在脊椎动物胚胎发育过程中，上颌突（maxillary prominences）内源自神经嵴（neural crest）的间充质细胞（mesenchymal cells）会经历精准协调的增殖与分化过程，最终形成牙齿、次生腭（secondary palate）等一系列颅面结构（craniofacial structures）。然而，支撑这一复杂过程的转录调控网络（transcriptional regulatory networks）尚未被完全阐明。本研究整合了批量RNA测序（bulk RNA-Seq）与单细胞RNA测序（single-cell RNA-Seq）技术，对小鼠上颌突从胚胎第10.5天（E10.5）至第14.5天（E14.5）的发育过程中的转录组动态变化进行了全面表征。本研究鉴定出了代表不同发育状态的间充质细胞群，并推导了其发育轨迹，证实腭向与牙向间充质谱系的细胞命运分化发生于E11.5时期。本研究进一步鉴定了与上颌突细胞命运转变相关的核心转录调控因子，并推导了由这些因子介导的基因调控网络（gene regulatory networks）。此外，本研究证实叉头框P1（Foxp1）可调控参与骨骼与软骨发育的基因，且其对于高效成骨（osteogenesis）过程不可或缺。综上，本研究为从系统层面解析颅面形态发生（craniofacial morphogenesis）与发育异常提供了丰富的研究资源与重要的理论见解。本数据集包含E10.5、E11.5、E12.5、E14.5小鼠胚胎上颌突组织的单细胞RNA测序数据。