Huang 黄文斌 Wenbin, Qian 钱振伟 Zhenwei, Zhang 张杰铌 Jieni, Ding 丁毅 Yi, Wang 王斌 Bin, Lin 林久祥 Jiuxiang, Zhang 张先念 Xiannian, Zhao 赵华翔 Huaxiang, Chen 陈峰 Feng
Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing 100081, China.
Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an 710004, China.
Genomics Proteomics Bioinformatics. 2025 May 10;23(1). doi: 10.1093/gpbjnl/qzaf013.
Cleft palate is one of the most common congenital craniofacial disorders that affects children's appearance and oral functions. Investigating the transcriptomes during palatogenesis is crucial for understanding the etiology of this disorder and facilitating prenatal molecular diagnosis. However, there is limited knowledge about the single-cell differentiation dynamics during mid-palatogenesis and late-palatogenesis, specifically regarding the subpopulations and developmental trajectories of periderm, a rare but critical cell population. Here, we explored the single-cell landscape of mouse developing palates from embryonic day (E) 10.5 to E16.5. We systematically depicted the single-cell transcriptomes of mesenchymal and epithelial cells during palatogenesis, including subpopulations and differentiation dynamics. Additionally, we identified four subclusters of palatal periderm and constructed two distinct trajectories of cell fates for periderm cells. Our findings reveal that claudin-family coding genes and Arhgap29 play a role in the non-stick function of the periderm before the palatal shelves contact, and Pitx2 mediates the adhesion of periderm during the contact of opposing palatal shelves. Furthermore, we demonstrate that epithelial-mesenchymal transition (EMT), apoptosis, and migration collectively contribute to the degeneration of periderm cells in the medial epithelial seam. Taken together, our study suggests a novel model of periderm development during palatogenesis and delineates the cellular and molecular transitions in periderm cell determination.
腭裂是最常见的先天性颅面疾病之一，会影响儿童的外貌和口腔功能。研究腭发育过程中的转录组对于理解该疾病的病因和促进产前分子诊断至关重要。然而，关于腭发育中期和晚期的单细胞分化动态，特别是关于周皮（一种罕见但关键的细胞群体）的亚群和发育轨迹，我们了解的还很有限。在这里，我们探索了从胚胎第10.5天（E10.5）到E16.5小鼠发育中腭的单细胞图谱。我们系统地描绘了腭发育过程中间充质和上皮细胞的单细胞转录组，包括亚群和分化动态。此外，我们鉴定出腭周皮的四个亚簇，并构建了周皮细胞的两种不同的细胞命运轨迹。我们的研究结果表明，紧密连接蛋白家族编码基因和Arhgap29在腭突接触前周皮的不粘连功能中发挥作用，而Pitx2在相对的腭突接触期间介导周皮的粘附。此外，我们证明上皮-间充质转化（EMT）、细胞凋亡和迁移共同导致内侧上皮缝中周皮细胞的退化。综上所述，我们的研究提出了一种腭发育过程中周皮发育的新模型，并描绘了周皮细胞确定过程中的细胞和分子转变。
