Gu Xiuge, Wei Wei, Wu Chuan, Sun Jing, Wu Xiaoshan, Shen Zongshan, Zhou Hanzhang, Zhang Chunmei, Wang Jinsong, Hu Lei, Chen Suwen, Zhang Yuanyuan, Wang Songlin, Zhang Ran
Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Beijing Laboratory of Oral Health and Beijing Stomatological Hospital, Department of Biochemistry and Molecular Biology, Capital Medical University School of Basic Medical Sciences, Capital Medical University, Beijing, China.
Academician Workstation for Oral-Maxillofacial Regenerative Medicine, Central South University, Changsha, China.
Int J Oral Sci. 2025 May 9;17(1):38. doi: 10.1038/s41368-025-00375-7.
The regulatory processes in developmental biology research are significantly influenced by long non-coding RNAs (lncRNAs). However, the dynamics of lncRNA expression during human tooth development remain poorly understood. In this research, we examined the lncRNAs present in the dental epithelium (DE) and dental mesenchyme (DM) at the late bud, cap, and early bell stages of human fetal tooth development through bulk RNA sequencing. Developmental regulators co-expressed with neighboring lncRNAs were significantly enriched in odontogenesis. Specific lncRNAs expressed in the DE and DM, such as PANCR, MIR205HG, DLX6-AS1, and DNM3OS, were identified through a combination of bulk RNA sequencing and single-cell analysis. Further subcluster analysis revealed lncRNAs specifically expressed in important regions of the tooth germ, such as the inner enamel epithelium and coronal dental papilla (CDP). Functionally, we demonstrated that CDP-specific DLX6-AS1 enhanced odontoblastic differentiation in human tooth germ mesenchymal cells and dental pulp stem cells. These findings suggest that lncRNAs could serve as valuable cell markers for tooth development and potential therapeutic targets for tooth regeneration.
长链非编码RNA（lncRNAs）对发育生物学研究中的调控过程有显著影响。然而，人类牙齿发育过程中lncRNA表达的动态变化仍知之甚少。在本研究中，我们通过大量RNA测序，检测了人类胎儿牙齿发育的晚蕾期、帽状期和早钟状期牙上皮（DE）和牙间充质（DM）中存在的lncRNAs。与相邻lncRNAs共表达的发育调节因子在牙发生过程中显著富集。通过大量RNA测序和单细胞分析相结合的方法，鉴定出了在DE和DM中表达的特定lncRNAs，如PANCR、MIR205HG、DLX6-AS1和DNM3OS。进一步的亚群分析揭示了在牙胚重要区域特异性表达的lncRNAs，如内釉上皮和冠状牙乳头（CDP）。在功能上，我们证明了CDP特异性的DLX6-AS1增强了人类牙胚间充质细胞和牙髓干细胞的成牙本质细胞分化。这些发现表明，lncRNAs可作为牙齿发育的有价值的细胞标志物和牙齿再生的潜在治疗靶点。
