Mapping a differentiation architecture for hard tissue mineralization with large-scale single-cell atlases
- 1Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine, Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China
- 2Medical Research Institute, School of Medicine, Wuhan University, Wuhan, China
- 3Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China
Abstract
Mineralization is a critical process in the formation of hard tissues such as bones and teeth, yet the cellular mechanisms underlying this process remain incompletely understood. To address this, we constructed a comprehensive single-cell atlas of tooth development, integrating data from 261,929 cells across 15 projects and encompassing both odontogenesis and amelogenesis. We developed a novel algorithm, TrajDTW, to identify genes with concordant trajectory dynamics across these large-scale datasets, allowing us to detect robust developmental signals. To define a shared mineralization trajectory architecture, we then integrated our tooth atlas with a previously constructed bone atlas. Applying TrajDTW to this combined resource revealed common molecular pathways governing the formation of distinct hard tissues, including bone, enamel, and dentin. Furthermore, cross-species analysis between human and mouse data uncovered cross-species conserved mesenchymal/odontoblast programs. This study provides an unprecedented resource for developmental biology and defines a molecular framework for mineralization that is shared across tissues and species. Author summary: The fundamental genetic rules governing hard tissue formation have long been elusive. In this study, we define a shared mineralization trajectory architecture by creating the most comprehensive single-cell atlas of tooth development to date. We developed a novel algorithm to identify trajectory-concordant gene programs across large-scale datasets and applied it to integrate our tooth atlas with an existing bone atlas. This integrated, cross-species analysis pinpointed the common molecular machinery directing hard-tissue formation. Our work provides an unprecedented resource and a powerful analytical framework, laying the foundation for new regenerative strategies aimed at treating skeletal and dental disorders.
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BibTeX
@article{han2026mapping,
title = {{Mapping a differentiation architecture for hard tissue mineralization with large-scale single-cell atlases}},
author = {Litian Han and Yiqian Yu and Mengge Feng and Zishu Lin and Yulan Wang and Ting Xia and Qihang Fan and Huan Liu and Yan Wei and Yufeng Zhang},
journal = {PLOS Computational Biology},
year = {2026},
month = sep,
doi = {10.1371/journal.pcbi.1014788},
url = {https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1014788},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Mapping a differentiation architecture for hard tissue mineralization with large-scale single-cell atlases
AU - Litian Han
AU - Yiqian Yu
AU - Mengge Feng
AU - Zishu Lin
AU - Yulan Wang
AU - Ting Xia
AU - Qihang Fan
AU - Huan Liu
AU - Yan Wei
AU - Yufeng Zhang
PY - 2026
DA - 2026/09/21
JO - PLOS Computational Biology
DO - 10.1371/journal.pcbi.1014788
UR - https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1014788
AB - Mineralization is a critical process in the formation of hard tissues such as bones and teeth, yet the cellular mechanisms underlying this process remain incompletely understood. To address this, we constructed a comprehensive single-cell atlas of tooth development, integrating data from 261,929 cells across 15 projects and encompassing both odontogenesis and amelogenesis. We developed a novel algorithm, TrajDTW, to identify genes with concordant trajectory dynamics across these large-scale datasets, allowing us to detect robust developmental signals. To define a shared mineralization trajectory architecture, we then integrated our tooth atlas with a previously constructed bone atlas. Applying TrajDTW to this combined resource revealed common molecular pathways governing the formation of distinct hard tissues, including bone, enamel, and dentin. Furthermore, cross-species analysis between human and mouse data uncovered cross-species conserved mesenchymal/odontoblast programs. This study provides an unprecedented resource for developmental biology and defines a molecular framework for mineralization that is shared across tissues and species. Author summary: The fundamental genetic rules governing hard tissue formation have long been elusive. In this study, we define a shared mineralization trajectory architecture by creating the most comprehensive single-cell atlas of tooth development to date. We developed a novel algorithm to identify trajectory-concordant gene programs across large-scale datasets and applied it to integrate our tooth atlas with an existing bone atlas. This integrated, cross-species analysis pinpointed the common molecular machinery directing hard-tissue formation. Our work provides an unprecedented resource and a powerful analytical framework, laying the foundation for new regenerative strategies aimed at treating skeletal and dental disorders.
SN - 1553-7358
ER -