{
  "abstract": "The lung consists of two anatomically distinct compartments: the airways and the alveoli. Although airway epithelial stem cells are known to mobilize for alveolar regeneration, whether alveolar cells can reciprocally traverse these anatomical boundaries and contribute to bronchial repair remains unclear1–4. Here we developed dual-recombinase-mediated lineage-tracing techniques in mice to demonstrate that alveolar type 2 (AT2) cells migrate into injured bronchioles and transdifferentiate into club cells and ciliated cells, thereby actively contributing to airway regeneration. Mechanistically, after bronchial injury, infiltrating immune cells secrete SPP1, establishing a chemotactic gradient directing cell migration. Peribronchiolar AT2 cells sense this SPP1 signal through the integrin ITGB1 and migrate towards the injured bronchioles. On arrival, these migrated AT2 cells receive Notch ligands from resident ciliated cells, leading to Notch pathway activation, which in turn drives their transdifferentiation into club cells. This transdifferentiation process is accompanied by an intermediate stage marked by Cldn4 expression. Functional blockade of either SPP1 or ITGB1 impairs AT2 cell migration, whereas inhibition of Notch signalling prevents their transdifferentiation into club cells. Collectively, our findings reveal a cross-compartmental cellular mechanism for bronchiolar epithelial repair, expanding the current understanding of lung regenerative plasticity and potentially informing therapeutic strategies for airway injury.",
  "abstract_shown": true,
  "affiliations": [
    "Zhejiang Key Laboratory of Signaling Mechanisms in Tumor Progression and Intervention, School of Life Science, Hangzhou Institute for Advanced Study, Hangzhou, University of Chinese Academy of Sciences, Hangzhou, China",
    "CAS CEMCS-CUHK Joint Laboratory, New Cornerstone Science Laboratory, Key Laboratory of Multi-Cell Systems, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China",
    "School of Life Science and Technology, ShanghaiTech University, Shanghai, China",
    "Department of Pulmonary and Critical Care Medicine, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China",
    "Shanghai Key Laboratory of Lung Inflammation and Injury, Shanghai, China",
    "CAS CEMCS-CUHK Joint Laboratory, Department of Chemical Pathology, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 18,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Kuo Liu"
    },
    {
      "affs": [
        1
      ],
      "name": "Zixin Liu",
      "orcid": "0000-0002-1085-8911"
    },
    {
      "affs": [
        2
      ],
      "name": "Xinfeng Meng",
      "orcid": "0000-0002-3000-8375"
    },
    {
      "affs": [
        1
      ],
      "name": "Muxue Tang",
      "orcid": "0009-0000-2325-3666"
    },
    {
      "affs": [
        2
      ],
      "name": "Fanglin Di",
      "orcid": "0009-0008-1169-3160"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhongxiao Wang",
      "orcid": "0009-0007-5895-4789"
    },
    {
      "affs": [
        3
      ],
      "name": "Chenfei Li",
      "orcid": "0000-0003-3906-4098"
    },
    {
      "affs": [
        1
      ],
      "name": "Shan Yang",
      "orcid": "0009-0007-9549-753X"
    },
    {
      "affs": [
        1
      ],
      "name": "Yanli Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Xueying Yang",
      "orcid": "0009-0005-1205-4211"
    },
    {
      "affs": [
        1
      ],
      "name": "Zan Lv",
      "orcid": "0000-0001-9743-4419"
    },
    {
      "affs": [
        0
      ],
      "name": "Xufeng Li",
      "orcid": "0000-0002-2666-3502"
    },
    {
      "affs": [
        1
      ],
      "name": "Hengwei Jin",
      "orcid": "0009-0001-3441-9542"
    },
    {
      "affs": [
        1
      ],
      "name": "Wenjuan Pu",
      "orcid": "0000-0001-5155-5178"
    },
    {
      "affs": [
        1
      ],
      "name": "Huan Zhao",
      "orcid": "0000-0001-6319-949X"
    },
    {
      "affs": [
        3
      ],
      "name": "Feng Li",
      "orcid": "0000-0002-0646-6560"
    },
    {
      "affs": [
        1,
        4
      ],
      "name": "Pengfei Sui",
      "orcid": "0000-0002-8140-7050"
    },
    {
      "affs": [
        0,
        1,
        2,
        5
      ],
      "name": "Bin Zhou",
      "orcid": "0000-0001-5278-5522"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/83cw2etbf0s39.bib",
  "cited_by": 1,
  "doi": "10.1038/s41586-026-11127-w",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13736204/",
  "id": "83cw2etbf0s39",
  "issns": [
    "0028-0836",
    "1476-4687"
  ],
  "landing_url": "https://doi.org/10.1038/s41586-026-11127-w",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
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      "openalex",
      "2740|Neonatal Respiratory Health Research"
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  "openalex": "W7220848820",
  "pdf_url": null,
  "pmcid": "PMC13736204",
  "pmid": "42844469",
  "published": "2026-10-07",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/83cw2etbf0s39.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T12:21:43Z",
      "native_id": "PMC13736204",
      "source": "pmc",
      "url": "https://doi.org/10.1038/s41586-026-11127-w"
    }
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2740|Neonatal Respiratory Health Research",
      "subfield": "general"
    }
  ],
  "title": "Alveolar stem cells transdifferentiate to drive bronchiolar regeneration",
  "title_text": "Alveolar stem cells transdifferentiate to drive bronchiolar regeneration",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:21:43Z",
  "url": "https://research.draconitic.com/paper/83cw2etbf0s39",
  "venue": "Nature",
  "versions": []
}