{
  "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.",
  "abstract_shown": true,
  "affiliations": [
    "Key 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",
    "Medical Research Institute, School of Medicine, Wuhan University, Wuhan, China",
    "Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Litian Han"
    },
    {
      "affs": [
        1
      ],
      "name": "Yiqian Yu"
    },
    {
      "affs": [
        2
      ],
      "name": "Mengge Feng"
    },
    {
      "name": "Zishu Lin"
    },
    {
      "name": "Yulan Wang"
    },
    {
      "name": "Ting Xia"
    },
    {
      "name": "Qihang Fan"
    },
    {
      "name": "Huan Liu"
    },
    {
      "name": "Yan Wei"
    },
    {
      "name": "Yufeng Zhang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/17pn9wbdh4s58.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.pcbi.1014788",
  "fulltext_url": "https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1014788",
  "id": "17pn9wbdh4s58",
  "issns": [
    "1553-7358"
  ],
  "landing_url": "https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1014788",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Single-cell and spatial transcriptomics"
    ],
    [
      "plos",
      "/Biology and life sciences/Anatomy/Biological tissue/Connective tissue/Connective tissue cells/Odontoblasts"
    ],
    [
      "plos",
      "/Biology and life sciences/Anatomy/Biological tissue/Epithelium/Epithelial cells/Ameloblasts"
    ],
    [
      "plos",
      "/Biology and life sciences/Anatomy/Digestive system/Teeth"
    ],
    [
      "plos",
      "/Biology and life sciences/Anatomy/Head/Jaw/Teeth"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cell processes/Cell cycle and cell division"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Connective tissue cells/Odontoblasts"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Epithelial cells/Ameloblasts"
    ],
    [
      "plos",
      "/Biology and life sciences/Computational biology/Genome analysis/Gene ontologies"
    ],
    [
      "plos",
      "/Biology and life sciences/Developmental biology/Cell differentiation"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Gene expression"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Genomics/Genome analysis/Gene ontologies"
    ],
    [
      "plos",
      "/Biology and life sciences/Molecular biology/Molecular biology techniques/Marker genes"
    ],
    [
      "plos",
      "/Medicine and health sciences/Anatomy/Biological tissue/Connective tissue/Connective tissue cells/Odontoblasts"
    ],
    [
      "plos",
      "/Medicine and health sciences/Anatomy/Biological tissue/Epithelium/Epithelial cells/Ameloblasts"
    ],
    [
      "plos",
      "/Medicine and health sciences/Anatomy/Digestive system/Teeth"
    ],
    [
      "plos",
      "/Medicine and health sciences/Anatomy/Head/Jaw/Teeth"
    ],
    [
      "plos",
      "/Research and analysis methods/Molecular biology techniques/Marker genes"
    ]
  ],
  "openalex": "W7213939084",
  "pdf_url": "https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1014788&type=printable",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-21",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/17pn9wbdh4s58.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:43Z",
      "native_id": "10.1371/journal.pcbi.1014788",
      "source": "plos",
      "url": "https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1014788"
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  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "plos:anatomy",
      "subfield": "physiology"
    }
  ],
  "title": "Mapping a differentiation architecture for hard tissue mineralization with large-scale single-cell atlases",
  "title_text": "Mapping a differentiation architecture for hard tissue mineralization with large-scale single-cell atlases",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:43Z",
  "url": "https://research.draconitic.com/paper/17pn9wbdh4s58",
  "venue": "PLOS Computational Biology",
  "versions": []
}