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.
Humans ; RNA, Long Noncoding/metabolism* ; Odontogenesis/genetics* ; Tooth Germ/embryology* ; Cell Differentiation ; Gene Expression Regulation, Developmental ; Mesoderm/metabolism* ; Tooth/embryology* ; Gene Expression Profiling ; Sequence Analysis, RNA ; Dental Pulp/cytology*

Understanding the pattern and molecular mechanisms of tooth, maxilla and mandible development is the prerequisite for studying their regeneration. Tooth development can be divided into three stages: bud-bell stage, tooth crown development stage and tooth root development stage. During these processes, key genes show spatial and temporal expression pattern. Tooth development is a complex process involving interactions between dental epithelium and mesenchyme, precise regulations of enamel knots in cusp patterning, as well as successful eruption into the oral cavity under proper biomechanical stress and signaling transductions. The development of tooth, maxilla and mandible, all of which originate from the first branchial arch, is independent and regulates each other to form a whole during development. Any developmental defects of them will ultimately cause defects to the others. In this paper, we briefly reviewed the development of tooth, maxilla and mandible, proposed that the homeostasis of microenvironment is critical for their development. Moreover, we reviewed the role of Meckel’s cartilage, a special structure and signaling mechanism during mandible development. At last, we proposed an integrated development model of tooth, maxilla and mandible. We also hope that the regeneration of fully functional tooth, maxilla and mandible in human can be achieved based on fundamental knowledge we have gained so far.

Objective To investigate the diagnostic value of PIgP/SC in diagnosis of primary hepatic cancer.Methods 58 patients with primary hepatic cancer,60 patients with liver cirrhosis and 60 healthy volunteers were studied.4 ml fasting venous blood was collected from all subjects.Serum level of AFP was detected with electrochemical chemiluminescence immunoassay system and plasma PIgR/SC level was detected by ELISA method.The level of PIgR/SC and AFP was detected at one week after surgical resection in patients with hepatic cancer.Results The levels of AFP and PIgR/SC in the three groups were significantly different (P＜0.01),and PIgR/SC was higher than that in patients with cirrhosis and volunteers (P＜0.01).There was no significant difference between patients with liver cirrhosis and liver cirrhosis(P＞0.05).AFP was higher in patients with HCC than patients with cirrhosis and volunteers.AFP was higher in patients with cirrhosis than volunteers,and the difference was statistically significant(P＜0.01).Sensitivity of PIgR/SC and AFP was 89.3％ and 54.8％,specificity was 84.6％ and 91％,Youden index was 0.751 and 0.458,AUC was 0.920 and 0.761,respectively.There was significant difference in AUC (Z=3.251,P＜0.05) of the two detection indexes for detection of primary hepatic cancer.Conclusion The value of PIgR/SC in diagnosis of primary liver cancer may by higher than that of AFP.