The landscape of cell regulatory and communication networks in the human dental follicle

IntroductionThe dental follicle localizes the surrounding enamel organ and dental papilla of the developing tooth germ during the embryonic stage. It can differentiate and develop to form the periodontal ligament, cementum, and alveolar bone tissues. Postnatally, the dental follicle gradually degene...

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Main Authors: Jia-Ning Liu, Jiong-Yi Tian, Lu Liu, Yuan Cao, Xiao Lei, Xiao-Hui Zhang, Zi-Qi Zhang, Jun-Xi He, Chen-Xi Zheng, Chao Ma, Sheng-Feng Bai, Bing-Dong Sui, Fang Jin, Ji Chen
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-02-01
Series:Frontiers in Bioengineering and Biotechnology
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Online Access:https://www.frontiersin.org/articles/10.3389/fbioe.2025.1535245/full
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author Jia-Ning Liu
Jia-Ning Liu
Jiong-Yi Tian
Lu Liu
Lu Liu
Yuan Cao
Yuan Cao
Xiao Lei
Xiao Lei
Xiao-Hui Zhang
Xiao-Hui Zhang
Zi-Qi Zhang
Zi-Qi Zhang
Jun-Xi He
Jun-Xi He
Chen-Xi Zheng
Chao Ma
Sheng-Feng Bai
Bing-Dong Sui
Fang Jin
Ji Chen
Ji Chen
author_facet Jia-Ning Liu
Jia-Ning Liu
Jiong-Yi Tian
Lu Liu
Lu Liu
Yuan Cao
Yuan Cao
Xiao Lei
Xiao Lei
Xiao-Hui Zhang
Xiao-Hui Zhang
Zi-Qi Zhang
Zi-Qi Zhang
Jun-Xi He
Jun-Xi He
Chen-Xi Zheng
Chao Ma
Sheng-Feng Bai
Bing-Dong Sui
Fang Jin
Ji Chen
Ji Chen
author_sort Jia-Ning Liu
collection DOAJ
description IntroductionThe dental follicle localizes the surrounding enamel organ and dental papilla of the developing tooth germ during the embryonic stage. It can differentiate and develop to form the periodontal ligament, cementum, and alveolar bone tissues. Postnatally, the dental follicle gradually degenerates, but some parts of the dental follicle remain around the impacted tooth. However, the specific cellular components and the intricate regulatory mechanisms governing the postnatal development and biological function of the dental follicle have not been completely understood.MethodsWe analyzed dental follicles with single-cell RNA sequencing (scRNA-seq) to reveal their cellular constitution molecular signatures by cell cycle analysis, scenic analysis, gene enrichment analysis, and cell communication analysis.ResultsTen cell clusters were identified with differential characteristics, among which immune and vessel-related cells, as well as a stem cell population, were revealed as the main cell types. Gene regulatory networks (GRNs) were established and defined four regulon modules underlying dental tissue development and microenvironmental regulation, including vascular and immune responses. Cell–cell communication analysis unraveled crosstalk between vascular and immune cell components in orchestrating dental follicle biological activities, potentially based on COLLAGAN-CD44 ligand–receptor pairs, as well as ANGPTL1-ITGA/ITGB ligand–receptor pairs.ConclusionWe establish a landscape of cell regulatory and communication networks in the human dental follicle, providing mechanistic insights into the cellular regulation and interactions in the complex dental follicle tissue microenvironment.
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spelling doaj-art-569d03da38b84748a196ab62cd9e4f652025-02-05T07:32:35ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852025-02-011310.3389/fbioe.2025.15352451535245The landscape of cell regulatory and communication networks in the human dental follicleJia-Ning Liu0Jia-Ning Liu1Jiong-Yi Tian2Lu Liu3Lu Liu4Yuan Cao5Yuan Cao6Xiao Lei7Xiao Lei8Xiao-Hui Zhang9Xiao-Hui Zhang10Zi-Qi Zhang11Zi-Qi Zhang12Jun-Xi He13Jun-Xi He14Chen-Xi Zheng15Chao Ma16Sheng-Feng Bai17Bing-Dong Sui18Fang Jin19Ji Chen20Ji Chen21State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi’an, Shaanxi, ChinaState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Diseases, Department of Orthodontics, School of Stomatology, The Fourth Military Medical University, Xi’an, Shaanxi, ChinaState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi’an, Shaanxi, ChinaState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi’an, Shaanxi, ChinaState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Diseases, Department of Orthodontics, School of Stomatology, The Fourth Military Medical University, Xi’an, Shaanxi, ChinaState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi’an, Shaanxi, ChinaState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Diseases, Department of Orthodontics, School of Stomatology, The Fourth Military Medical University, Xi’an, Shaanxi, ChinaState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi’an, Shaanxi, ChinaState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Diseases, Department of Orthodontics, School of Stomatology, The Fourth Military Medical University, Xi’an, Shaanxi, ChinaState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi’an, Shaanxi, ChinaState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Diseases, Department of Orthodontics, School of Stomatology, The Fourth Military Medical University, Xi’an, Shaanxi, ChinaState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi’an, Shaanxi, ChinaState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Diseases, Department of Orthodontics, School of Stomatology, The Fourth Military Medical University, Xi’an, Shaanxi, ChinaState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi’an, Shaanxi, ChinaState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Diseases, Department of Orthodontics, School of Stomatology, The Fourth Military Medical University, Xi’an, Shaanxi, ChinaState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi’an, Shaanxi, ChinaState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi’an, Shaanxi, ChinaState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi’an, Shaanxi, ChinaState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi’an, Shaanxi, ChinaState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Diseases, Department of Orthodontics, School of Stomatology, The Fourth Military Medical University, Xi’an, Shaanxi, ChinaState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi’an, Shaanxi, ChinaDepartment of Oral Implantology, School of Stomatology, The Fourth Military Medical University, Xi’an, Shaanxi, ChinaIntroductionThe dental follicle localizes the surrounding enamel organ and dental papilla of the developing tooth germ during the embryonic stage. It can differentiate and develop to form the periodontal ligament, cementum, and alveolar bone tissues. Postnatally, the dental follicle gradually degenerates, but some parts of the dental follicle remain around the impacted tooth. However, the specific cellular components and the intricate regulatory mechanisms governing the postnatal development and biological function of the dental follicle have not been completely understood.MethodsWe analyzed dental follicles with single-cell RNA sequencing (scRNA-seq) to reveal their cellular constitution molecular signatures by cell cycle analysis, scenic analysis, gene enrichment analysis, and cell communication analysis.ResultsTen cell clusters were identified with differential characteristics, among which immune and vessel-related cells, as well as a stem cell population, were revealed as the main cell types. Gene regulatory networks (GRNs) were established and defined four regulon modules underlying dental tissue development and microenvironmental regulation, including vascular and immune responses. Cell–cell communication analysis unraveled crosstalk between vascular and immune cell components in orchestrating dental follicle biological activities, potentially based on COLLAGAN-CD44 ligand–receptor pairs, as well as ANGPTL1-ITGA/ITGB ligand–receptor pairs.ConclusionWe establish a landscape of cell regulatory and communication networks in the human dental follicle, providing mechanistic insights into the cellular regulation and interactions in the complex dental follicle tissue microenvironment.https://www.frontiersin.org/articles/10.3389/fbioe.2025.1535245/fulldental folliclesingle-cell RNA sequencinggene regulatory networkscell–cell communicationvasculatureimmune
spellingShingle Jia-Ning Liu
Jia-Ning Liu
Jiong-Yi Tian
Lu Liu
Lu Liu
Yuan Cao
Yuan Cao
Xiao Lei
Xiao Lei
Xiao-Hui Zhang
Xiao-Hui Zhang
Zi-Qi Zhang
Zi-Qi Zhang
Jun-Xi He
Jun-Xi He
Chen-Xi Zheng
Chao Ma
Sheng-Feng Bai
Bing-Dong Sui
Fang Jin
Ji Chen
Ji Chen
The landscape of cell regulatory and communication networks in the human dental follicle
Frontiers in Bioengineering and Biotechnology
dental follicle
single-cell RNA sequencing
gene regulatory networks
cell–cell communication
vasculature
immune
title The landscape of cell regulatory and communication networks in the human dental follicle
title_full The landscape of cell regulatory and communication networks in the human dental follicle
title_fullStr The landscape of cell regulatory and communication networks in the human dental follicle
title_full_unstemmed The landscape of cell regulatory and communication networks in the human dental follicle
title_short The landscape of cell regulatory and communication networks in the human dental follicle
title_sort landscape of cell regulatory and communication networks in the human dental follicle
topic dental follicle
single-cell RNA sequencing
gene regulatory networks
cell–cell communication
vasculature
immune
url https://www.frontiersin.org/articles/10.3389/fbioe.2025.1535245/full
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