A single-cell interactome of human tooth germ from growing third molar elucidates signaling networks regulating dental development
Abstract Background Development of dental tissue is regulated by extensive cell crosstalk based on various signaling molecules, such as bone morphogenetic protein (BMP) and fibroblast growth factor (FGF) pathways. However, an intact network of the intercellular regulation is still lacking. Result To...
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| Format: | Article |
| Language: | English |
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BMC
2021-10-01
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| Series: | Cell & Bioscience |
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| Online Access: | https://doi.org/10.1186/s13578-021-00691-5 |
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doaj-a5db4267d501400c8323733b1f336708 |
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Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Yueqi Shi Yejia Yu Yuqiong Zhou Jun Zhao Wenjie Zhang Duohong Zou Weichen Song Shaoyi Wang |
| spellingShingle |
Yueqi Shi Yejia Yu Yuqiong Zhou Jun Zhao Wenjie Zhang Duohong Zou Weichen Song Shaoyi Wang A single-cell interactome of human tooth germ from growing third molar elucidates signaling networks regulating dental development Cell & Bioscience Tooth germ Single-cell sequencing Signaling pathway Osteoblast BMP |
| author_facet |
Yueqi Shi Yejia Yu Yuqiong Zhou Jun Zhao Wenjie Zhang Duohong Zou Weichen Song Shaoyi Wang |
| author_sort |
Yueqi Shi |
| title |
A single-cell interactome of human tooth germ from growing third molar elucidates signaling networks regulating dental development |
| title_short |
A single-cell interactome of human tooth germ from growing third molar elucidates signaling networks regulating dental development |
| title_full |
A single-cell interactome of human tooth germ from growing third molar elucidates signaling networks regulating dental development |
| title_fullStr |
A single-cell interactome of human tooth germ from growing third molar elucidates signaling networks regulating dental development |
| title_full_unstemmed |
A single-cell interactome of human tooth germ from growing third molar elucidates signaling networks regulating dental development |
| title_sort |
single-cell interactome of human tooth germ from growing third molar elucidates signaling networks regulating dental development |
| publisher |
BMC |
| series |
Cell & Bioscience |
| issn |
2045-3701 |
| publishDate |
2021-10-01 |
| description |
Abstract Background Development of dental tissue is regulated by extensive cell crosstalk based on various signaling molecules, such as bone morphogenetic protein (BMP) and fibroblast growth factor (FGF) pathways. However, an intact network of the intercellular regulation is still lacking. Result To gain an unbiased and comprehensive view of this dental cell interactome, we applied single-cell RNA-seq on immature human tooth germ of the growing third molar, discovered refined cell subtypes, and applied multiple network analysis to identify the central signaling pathways. We found that immune cells made up over 80% of all tooth germ cells, which exhibited profound regulation on dental cells via Transforming growth factor-β, Tumor necrosis factor (TNF) and Interleukin-1. During osteoblast differentiation, expression of genes related to extracellular matrix and mineralization was continuously elevated by signals from BMP and FGF family. As for the self-renewal of apical papilla stem cell, BMP-FGFR1-MSX1 pathway directly regulated the G0-to-S cell cycle transition. We also confirmed that Colony Stimulating Factor 1 secreted from pericyte and TNF Superfamily Member 11 secreted from osteoblast regulated a large proportion of genes related to osteoclast transformation from macrophage and monocyte. Conclusions We constructed the intercellular signaling networks that regulated the essential developmental process of human tooth, which served as a foundation for future dental regeneration engineering and the understanding of oral pathology. |
| topic |
Tooth germ Single-cell sequencing Signaling pathway Osteoblast BMP |
| url |
https://doi.org/10.1186/s13578-021-00691-5 |
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doaj-a5db4267d501400c8323733b1f3367082021-10-03T11:45:45ZengBMCCell & Bioscience2045-37012021-10-0111111710.1186/s13578-021-00691-5A single-cell interactome of human tooth germ from growing third molar elucidates signaling networks regulating dental developmentYueqi Shi0Yejia Yu1Yuqiong Zhou2Jun Zhao3Wenjie Zhang4Duohong Zou5Weichen Song6Shaoyi Wang7Department of Oral Surgery, Shanghai Key Laboratory of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, College of Stomatology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong UniversityDepartment of Oral Surgery, Shanghai Key Laboratory of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, College of Stomatology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong UniversityDepartment of Oral Surgery, Shanghai Key Laboratory of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, College of Stomatology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong UniversityDepartment of Orthodontics, Shanghai Key Laboratory of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, College of Stomatology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong UniversityDepartment of Prosthodontics, Shanghai Key Laboratory of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, College of Stomatology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong UniversityDepartment of Oral Surgery, Shanghai Key Laboratory of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, College of Stomatology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong UniversityShanghai Mental Health Center, Shanghai Jiao Tong University School of MedicineDepartment of Oral Surgery, Shanghai Key Laboratory of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, College of Stomatology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong UniversityAbstract Background Development of dental tissue is regulated by extensive cell crosstalk based on various signaling molecules, such as bone morphogenetic protein (BMP) and fibroblast growth factor (FGF) pathways. However, an intact network of the intercellular regulation is still lacking. Result To gain an unbiased and comprehensive view of this dental cell interactome, we applied single-cell RNA-seq on immature human tooth germ of the growing third molar, discovered refined cell subtypes, and applied multiple network analysis to identify the central signaling pathways. We found that immune cells made up over 80% of all tooth germ cells, which exhibited profound regulation on dental cells via Transforming growth factor-β, Tumor necrosis factor (TNF) and Interleukin-1. During osteoblast differentiation, expression of genes related to extracellular matrix and mineralization was continuously elevated by signals from BMP and FGF family. As for the self-renewal of apical papilla stem cell, BMP-FGFR1-MSX1 pathway directly regulated the G0-to-S cell cycle transition. We also confirmed that Colony Stimulating Factor 1 secreted from pericyte and TNF Superfamily Member 11 secreted from osteoblast regulated a large proportion of genes related to osteoclast transformation from macrophage and monocyte. Conclusions We constructed the intercellular signaling networks that regulated the essential developmental process of human tooth, which served as a foundation for future dental regeneration engineering and the understanding of oral pathology.https://doi.org/10.1186/s13578-021-00691-5Tooth germSingle-cell sequencingSignaling pathwayOsteoblastBMP |