牙齿是发育研究的典范,包括上皮-间质转化和细胞分化。确定牙齿发育的基本因素和途径将有助于了解自然发育过程和骨骼等矿化组织的畸形。通过健康人类磨牙在胚胎阶段的蛋白质组学研究了时间依赖性蛋白质组的变化,从上限到早期钟声阶段。综合分析显示713种差异表达的蛋白质(DEP)表现出五种不同的时间表达模式。通过应用加权基因共表达网络分析(WGCNA),筛选了24种潜在的牙齿发育驱动蛋白,包括CHID1,RAP1GDS1,HAPLN3,AKAP12,WLS,GSS,DDAH1,CLSTN1,AFM,RBP1,AGO1,SET,HMGB2,HMGB1,ANP32A,SPON1,FREM1,C8B,PRPS2,FCHO2,PPP1R12A,GPALPP1、U2AF2和RCC2。然后,进一步比较了这些蛋白质的蛋白质组学和转录组学表达模式,辅以单细胞RNA测序(scRNA-seq)。总之,这项研究不仅提供了有关人类胚胎上皮和间充质细胞分化的分子复杂性的大量信息,而且为未来对牙齿发育的机理研究提供了宝贵的资源。
The tooth serves as an exemplary model for developmental studies, encompassing epithelial-mesenchymal transition and cell differentiation. The essential factors and pathways identified in tooth development will help understand the natural development process and the malformations of mineralized tissues such as skeleton. The time-dependent proteomic changes were investigated through the proteomics of healthy human molars during embryonic stages, ranging from the cap-to-early bell stage. A comprehensive analysis revealed 713 differentially expressed proteins (DEPs) exhibiting five distinct temporal expression patterns. Through the application of weighted gene co-expression network analysis (WGCNA), 24 potential driver proteins of tooth development were screened, including CHID1, RAP1GDS1, HAPLN3, AKAP12, WLS, GSS, DDAH1, CLSTN1, AFM, RBP1, AGO1, SET, HMGB2, HMGB1, ANP32A, SPON1, FREM1, C8B, PRPS2, FCHO2, PPP1R12A, GPALPP1, U2AF2, and RCC2. Then, the proteomics and transcriptomics expression patterns of these proteins were further compared, complemented by single-cell RNA-sequencing (scRNA-seq). In summary, this study not only offers a wealth of information regarding the molecular intricacies of human embryonic epithelial and mesenchymal cell differentiation but also serves as an invaluable resource for future mechanistic inquiries into tooth development.