Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China.
School of Stomatology, Southern Medical University, Guangzhou, 510515, China.
BMC Genomics. 2023 Apr 3;24(1):163. doi: 10.1186/s12864-023-09140-8.
Epithelium-mesenchymal interactions are involved in odontogenic processes. Previous studies have focused on the intracellular signalling regulatory network in tooth development, but the functions of extracellular regulatory molecules have remained unclear. This study aims to explore the gene profile of extracellular proteoglycans and their glycosaminoglycan chains potentially involved in dental epithelium-mesenchymal interactions using high-throughput sequencing to provide new understanding of early odontogenesis.
Whole transcriptome profiles of the mouse dental epithelium and mesenchyme were investigated by RNA sequencing (RNA-seq). A total of 1,281 and 1,582 differentially expressed genes were identified between the dental epithelium and mesenchyme at E11.5 and E13.5, respectively. Enrichment analysis showed that extracellular regions and ECM-receptor interactions were significantly enriched at both E11.5 and E13.5. Polymerase chain reaction analysis confirmed that the extracellular proteoglycan family exhibited distinct changes during epithelium-mesenchymal interactions. Most proteoglycans showed higher transcript levels in the dental mesenchyme, whereas only a few were upregulated in the epithelium at both stages. In addition, 9 proteoglycans showed dynamic expression changes between these two tissue compartments. Gpc4, Sdc2, Spock2, Dcn and Lum were expressed at higher levels in the dental epithelium at E11.5, whereas their expression was significantly higher in the dental mesenchyme at E13.5, which coincides with the odontogenic potential shift. Moreover, the glycosaminoglycan biosynthetic enzymes Ext1, Hs3st1/5, Hs6st2/3, Ndst3 and Sulf1 also exhibited early upregulation in the epithelium but showed markedly higher expression in the mesenchyme after the odontogenic potential shift.
This study reveals the dynamic expression profile of extracellular proteoglycans and their biosynthetic enzymes during the dental epithelium-mesenchymal interaction. This study offers new insight into the roles of extracellular proteoglycans and their distinct sulfation underlying early odontogenesis.
上皮-间充质相互作用参与牙发生过程。先前的研究集中在牙齿发育过程中的细胞内信号转导调控网络，但细胞外调节分子的功能仍不清楚。本研究旨在使用高通量测序探索可能参与牙上皮-间充质相互作用的细胞外蛋白聚糖及其糖胺聚糖链的基因谱，为早期牙发生提供新的认识。
通过 RNA 测序（RNA-seq）研究了小鼠牙上皮和间充质的全转录组谱。在 E11.5 和 E13.5 时，牙上皮和间充质之间分别鉴定出 1281 和 1582 个差异表达基因。富集分析表明，在 E11.5 和 E13.5 时，细胞外区和 ECM-受体相互作用均显著富集。聚合酶链反应分析证实，在外胚层-间充质相互作用过程中，细胞外蛋白聚糖家族发生了明显变化。大多数蛋白聚糖在牙间充质中表现出较高的转录水平，而在两个阶段上皮中仅有少数上调。此外，这两个组织隔室之间有 9 种蛋白聚糖表现出动态表达变化。Gpc4、Sdc2、Spock2、Dcn 和 Lum 在 E11.5 时在牙上皮中表达水平较高，而在 E13.5 时在牙间充质中的表达水平显著较高，这与牙发生潜能转移相吻合。此外，糖胺聚糖生物合成酶 Ext1、Hs3st1/5、Hs6st2/3、Ndst3 和 Sulf1 也在上皮中早期上调，但在牙发生潜能转移后在间充质中表达明显更高。
本研究揭示了牙上皮-间充质相互作用过程中外泌体蛋白聚糖及其生物合成酶的动态表达谱。本研究为细胞外蛋白聚糖及其在早期牙发生中独特的硫酸化作用提供了新的见解。
