Identification of GLDN^(^(+))odontogenic stem cells as crucial for human tooth development and regenerationOA
The dental papilla(DP)is essential for the development of dentin and pulp.The extensive cellular heterogeneity within the DP is a critical factor underlying the complex and precise formation of dental structures during odontogenesis.However,the critical cell types within human DP that play essential role in tooth development and regeneration remain largely uncharacterized.In this study,we analyzed the heterogeneity of human DP cells using single-cell sequencing and identified Gliomedin(GLDN)^(+)DP stem cells(DPSCs)were a group of progenitors at an early stage of tooth development and play a key role in the development of pulp and dentin.GLDN^(+)DPSCs strategically accumulate in human DP tissue near the interface of the newly formed dentin or pulp.Functional assays demonstrated that GLDN^(+)DPSCs exhibited enhanced self-renewal,migratory capacity,and odontogenic differentiation potential in vitro compared to GLDN-DPSCs.Moreover,GLDN^(+)DPSCs effectively induce the migration and tube formation of endothelial cells,which are essential for tooth development.The ectopic dental pulp regeneration model confirmed that GLDN^(+)DPSCs can regenerate a vascularized dental pulp structure with an odontoblast layer in vivo.Given their functional capabilities,this population of cells has been designated as GLDN^(+)odontogenic stem cells(OSCs).Mechanistically,GLDN is essential for maintaining the phenotype and function of GLDN^(+)OSCs through BMP5 signaling via autocrine and paracrine mechanisms.In conclusion,this study identifies a previously uncharacterized essential subpopulation of OSCs essential for dental pulp development and regeneration.
Chengcheng Liao;Jinglun Liu;Maojiao Li;Bingqian Yang;Yejia Yu;Jian Yang;Xiaoxia Su;Shixing Ma;Hanchao Li;Jingyi Zhang;Weidong Tian;Li Liao
State Key Laboratory of Oral Diseases&National Clinical Research Center for Oral Diseases&Engineering Research Center of Oral Translational Medicine,Ministry of Education&National Engineering Laboratory for Oral Regenerative Medicine,West China Hospital of Stomatology,Sichuan University,Chengdu,China Department of Oral and Maxillofacial Surgery,West China Hospital of Stomatology,Sichuan University,Chengdu,China Department of Orthodontics,Affiliated Stomatology Hospital of Zunyi Medical University,Zunyi,ChinaState Key Laboratory of Oral Diseases&National Clinical Research Center for Oral Diseases&Engineering Research Center of Oral Translational Medicine,Ministry of Education&National Engineering Laboratory for Oral Regenerative Medicine,West China Hospital of Stomatology,Sichuan University,Chengdu,China Department of Oral and Maxillofacial Surgery,West China Hospital of Stomatology,Sichuan University,Chengdu,ChinaState Key Laboratory of Oral Diseases&National Clinical Research Center for Oral Diseases&Engineering Research Center of Oral Translational Medicine,Ministry of Education&National Engineering Laboratory for Oral Regenerative Medicine,West China Hospital of Stomatology,Sichuan University,Chengdu,China Department of Oral and Maxillofacial Surgery,West China Hospital of Stomatology,Sichuan University,Chengdu,ChinaState Key Laboratory of Oral Diseases&National Clinical Research Center for Oral Diseases&Engineering Research Center of Oral Translational Medicine,Ministry of Education&National Engineering Laboratory for Oral Regenerative Medicine,West China Hospital of Stomatology,Sichuan University,Chengdu,China Department of Oral and Maxillofacial Surgery,West China Hospital of Stomatology,Sichuan University,Chengdu,ChinaState Key Laboratory of Oral Diseases&National Clinical Research Center for Oral Diseases&Engineering Research Center of Oral Translational Medicine,Ministry of Education&National Engineering Laboratory for Oral Regenerative Medicine,West China Hospital of Stomatology,Sichuan University,Chengdu,China Department of Oral and Maxillofacial Surgery,West China Hospital of Stomatology,Sichuan University,Chengdu,ChinaState Key Laboratory of Oral Diseases&National Clinical Research Center for Oral Diseases&Engineering Research Center of Oral Translational Medicine,Ministry of Education&National Engineering Laboratory for Oral Regenerative Medicine,West China Hospital of Stomatology,Sichuan University,Chengdu,China Department of Oral and Maxillofacial Surgery,West China Hospital of Stomatology,Sichuan University,Chengdu,ChinaState Key Laboratory of Oral Diseases&National Clinical Research Center for Oral Diseases&Engineering Research Center of Oral Translational Medicine,Ministry of Education&National Engineering Laboratory for Oral Regenerative Medicine,West China Hospital of Stomatology,Sichuan University,Chengdu,China Department of Oral and Maxillofacial Surgery,West China Hospital of Stomatology,Sichuan University,Chengdu,ChinaState Key Laboratory of Oral Diseases&National Clinical Research Center for Oral Diseases&Engineering Research Center of Oral Translational Medicine,Ministry of Education&National Engineering Laboratory for Oral Regenerative Medicine,West China Hospital of Stomatology,Sichuan University,Chengdu,China Department of Oral and Maxillofacial Surgery,West China Hospital of Stomatology,Sichuan University,Chengdu,China Stomatology Hospital,School of Stomatology,Zhejiang University School of Medicine,Zhejiang Provincial Clinical Research Center for Oral Diseases,Key Laboratory of Oral Biomedical Research of Zhejiang Province,Cancer Center of Zhejiang University,Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province,Hangzhou,ChinaState Key Laboratory of Oral Diseases&National Clinical Research Center for Oral Diseases&Engineering Research Center of Oral Translational Medicine,Ministry of Education&National Engineering Laboratory for Oral Regenerative Medicine,West China Hospital of Stomatology,Sichuan University,Chengdu,China Department of Oral and Maxillofacial Surgery,West China Hospital of Stomatology,Sichuan University,Chengdu,ChinaChengdu Shiliankangjian Biotechnology Co.Ltd,Chengdu,ChinaState Key Laboratory of Oral Diseases&National Clinical Research Center for Oral Diseases&Engineering Research Center of Oral Translational Medicine,Ministry of Education&National Engineering Laboratory for Oral Regenerative Medicine,West China Hospital of Stomatology,Sichuan University,Chengdu,China Department of Oral and Maxillofacial Surgery,West China Hospital of Stomatology,Sichuan University,Chengdu,ChinaState Key Laboratory of Oral Diseases&National Clinical Research Center for Oral Diseases&Engineering Research Center of Oral Translational Medicine,Ministry of Education&National Engineering Laboratory for Oral Regenerative Medicine,West China Hospital of Stomatology,Sichuan University,Chengdu,China Department of Oral and Maxillofacial Surgery,West China Hospital of Stomatology,Sichuan University,Chengdu,China
医药卫生
dental papilla dpdental papillacell typesdevelopment dentin pulpthecellular heterogeneitygliomedinself renewalsingle cell sequencing
《International Journal of Oral Science》 2026 (3)
P.386-400,15
supported by grants from the National Key Research and Development Program of China(2022YFA1104400)the National Natural Science Foundation of China(32271365,32471183,U21A20369)Sichuan Science and Technology program(2023YFS0151,2023YFS0056)the Fundamental Research Funds for the Central Universities(SCU2023D014)。
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