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International journal of oral science. 2025 May 9;17(1):38. doi: 10.1038/s41368-025-00375-7 Q110.82024

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

人牙发育过程中长链非编码RNA的特征分析及功能表征 翻译改进

Xiuge Gu  1, Wei Wei  1, Chuan Wu  1, Jing Sun  1, Xiaoshan Wu  1  2, Zongshan Shen  1  3, Hanzhang Zhou  4, Chunmei Zhang  1, Jinsong Wang  1, Lei Hu  1, Suwen Chen  5, Yuanyuan Zhang  5, Songlin Wang  6  7  8, Ran Zhang  9  10

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作者单位

  • 1 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.
  • 2 Academician Workstation for Oral-Maxillofacial Regenerative Medicine, Central South University, Changsha, China.
  • 3 Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China.
  • 4 Department of Oral Pathology, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, China.
  • 5 Department of Reproductive Regulation, Beijing Obstetrics and Gynecology Hospital, Beijing Maternal and Child Health Care Hospital, Capital Medical University, Beijing, China.
  • 6 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. slwang@ccmu.edu.cn.
  • 7 Academician Workstation for Oral-Maxillofacial Regenerative Medicine, Central South University, Changsha, China. slwang@ccmu.edu.cn.
  • 8 Laboratory of Homeostatic Medicine, School of Medicine, Southern University of Science and Technology, Shenzhen, China. slwang@ccmu.edu.cn.
  • 9 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. rani@bjmu.edu.cn.
  • 10 Department of Oral Pathology, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, China. rani@bjmu.edu.cn.

    • DOI: 10.1038/s41368-025-00375-7 PMID: 40346090

    摘要 中英对照阅读

    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.

    Keywords：long noncoding RNAs; tooth development

    在发育生物学研究中，长非编码RNA（lncRNAs）对调节过程产生了重要影响。然而，在人类牙齿发育过程中lncRNA的表达动态仍然知之甚少。在这项研究中，我们通过批量RNA测序技术检查了晚芽期、帽状期和早期铃铛阶段的人类胎儿牙齿发育中牙上皮（DE）和牙间质（DM）中的lncRNAs。与邻近lncRNAs共表达的发育调控因子在牙齿发生过程中显著富集。通过结合批量RNA测序和单细胞分析，我们确定了特异性表达于DE和DM的一些特定lncRNAs，如PANCR、MIR205HG、DLX6-AS1和DNM3OS等。进一步的亚簇分析揭示了一些在牙齿胚芽重要区域（如内釉上皮层和冠状牙乳头（CDP））中特异表达的lncRNAs。功能研究显示，CDP特异性DLX6-AS1能增强人类牙齿发育间质细胞和牙髓干细胞中的成牙本质细胞分化。这些发现表明lncRNA可能作为牙齿发育过程中有价值的细胞标志物，并且可能是牙齿再生治疗靶点。

    © 2025. The Author(s).

    关键词：长非编码RNA; 牙齿发育

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    期刊名：International journal of oral science

    缩写：INT J ORAL SCI

    ISSN：1674-2818

    e-ISSN：2049-3169

    IF/分区：10.8/Q1

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