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

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

doi:10.3389/fbioe.2025.1535245

Frontiers in Bioengineering and Biotechnology (Feb 2025)

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

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

Affiliations

Jia-Ning Liu: State 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, China
Jia-Ning Liu: State 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, China
Jiong-Yi Tian: State 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, China
Lu Liu: State 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, China
Lu Liu: State 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, China
Yuan Cao: State 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, China
Yuan Cao: State 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, China
Xiao Lei: State 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, China
Xiao Lei: State 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, China
Xiao-Hui Zhang: State 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, China
Xiao-Hui Zhang: State 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, China
Zi-Qi Zhang: State 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, China
Zi-Qi Zhang: State 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, China
Jun-Xi He: State 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, China
Jun-Xi He: State 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, China
Chen-Xi Zheng: State 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, China
Chao Ma: State 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, China
Sheng-Feng Bai: State 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, China
Bing-Dong Sui: State 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, China
Fang Jin: State 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, China
Ji Chen: State 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, China
Ji Chen: Department of Oral Implantology, School of Stomatology, The Fourth Military Medical University, Xi’an, Shaanxi, China

DOI: https://doi.org/10.3389/fbioe.2025.1535245
Journal volume & issue: Vol. 13

Abstract

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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.

Published in Frontiers in Bioengineering and Biotechnology

ISSN: 2296-4185 (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Technology: Chemical technology: Biotechnology
Website: http://www.frontiersin.org/bioengineering_and_biotechnology

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