Profiling and functional characterization of long noncoding RNAs during human tooth development

IF 10.8 1区医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

International Journal of Oral Science Pub Date : 2025-05-09 DOI:10.1038/s41368-025-00375-7

Xiuge Gu, Wei Wei, Chuan Wu, Jing Sun, Xiaoshan Wu, Zongshan Shen, Hanzhang Zhou, Chunmei Zhang, Jinsong Wang, Lei Hu, Suwen Chen, Yuanyuan Zhang, Songlin Wang, Ran Zhang

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Abstract

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.

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长链非编码rna在人类牙齿发育过程中的分析和功能表征

长链非编码rna （long non-coding rna, lncRNAs）对发育生物学研究中的调控过程有重要影响。然而，lncRNA在人类牙齿发育过程中的表达动态仍然知之甚少。在这项研究中，我们通过大量RNA测序检测了在人类胎儿牙齿发育的芽晚期、牙盖晚期和钟形早期，牙上皮（DE）和牙间质（DM）中存在的lncrna。与邻近lncrna共表达的发育调节因子在牙形成过程中显著富集。在DE和DM中表达的特异性lncrna，如PANCR、MIR205HG、DLX6-AS1和DNM3OS，通过大量RNA测序和单细胞分析相结合的方式被鉴定出来。进一步的亚聚类分析显示，lncrna特异性表达于牙胚的重要区域，如内牙釉质上皮和冠状牙乳头（CDP）。在功能上，我们证明了cdp特异性DLX6-AS1增强了人牙胚间充质细胞和牙髓干细胞的成牙细胞分化。这些发现表明lncrna可以作为牙齿发育的有价值的细胞标记物和牙齿再生的潜在治疗靶点。

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来源期刊

International Journal of Oral Science DENTISTRY, ORAL SURGERY & MEDICINE-

CiteScore

31.80

自引率

1.30%

发文量

审稿时长

>12 weeks

期刊介绍： The International Journal of Oral Science covers various aspects of oral science and interdisciplinary fields, encompassing basic, applied, and clinical research. Topics include, but are not limited to: Oral microbiology Oral and maxillofacial oncology Cariology Oral inflammation and infection Dental stem cells and regenerative medicine Craniofacial surgery Dental material Oral biomechanics Oral, dental, and maxillofacial genetic and developmental diseases Craniofacial bone research Craniofacial-related biomaterials Temporomandibular joint disorder and osteoarthritis The journal publishes peer-reviewed Articles presenting new research results and Review Articles offering concise summaries of specific areas in oral science.