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Malfunction of airway basal stem cells plays a crucial role in pathophysiology of tracheobronchopathia osteoplastica

Author

Listed:
  • Yue Hong

    (Shanghai Jiao Tong University Affiliated Sixth People’s Hospital)

  • Shan Shan

    (Shanghai Jiao Tong University Affiliated Sixth People’s Hospital)

  • Ye Gu

    (Tongji University Affiliated Shanghai Pulmonary Hospital)

  • Haidong Huang

    (Changhai Hospital, The Second Military Medical University)

  • Quncheng Zhang

    (Henan Provincial People’s Hospital)

  • Yang Han

    (Shanghai Jiao Tong University Affiliated Sixth People’s Hospital)

  • Yongpin Dong

    (The Second Military Medical University)

  • Zeyu Liu

    (Shanghai Jiao Tong University Affiliated Sixth People’s Hospital)

  • Moli Huang

    (Soochow University)

  • Tao Ren

    (Shanghai Jiao Tong University Affiliated Sixth People’s Hospital)

Abstract

Understanding disease-associated stem cell abnormality has major clinical implications for prevention and treatment of human disorders, as well as for regenerative medicine. Here we report a multifaceted study on airway epithelial stem cells in Tracheobronchopathia Osteochondroplastica (TO), an under-detected tracheobronchial disorder of unknown etiology and lack of specific treatment. Epithelial squamous metaplasia and heterotopic bone formation with abnormal cartilage proliferation and calcium deposits are key pathological hallmarks of this disorder, but it is unknown whether they are coincident or share certain pathogenic mechanisms in common. By functional evaluation and genome-wide profiling at both transcriptional and epigenetic levels, we reveal a role of airway basal cells in TO progression by acting as a repository of inflammatory and TGFβ-BMP signals, which contributes to both epithelial metaplasia and mesenchymal osteo-chondrogenesis via extracellular signaling and matrix remodeling. Restoration of microenvironment by cell correction or local pathway intervention may provide therapeutic benefits.

Suggested Citation

  • Yue Hong & Shan Shan & Ye Gu & Haidong Huang & Quncheng Zhang & Yang Han & Yongpin Dong & Zeyu Liu & Moli Huang & Tao Ren, 2022. "Malfunction of airway basal stem cells plays a crucial role in pathophysiology of tracheobronchopathia osteoplastica," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28903-7
    DOI: 10.1038/s41467-022-28903-7
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    References listed on IDEAS

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    1. Haotian Lin & Hong Ouyang & Jie Zhu & Shan Huang & Zhenzhen Liu & Shuyi Chen & Guiqun Cao & Gen Li & Robert A. J. Signer & Yanxin Xu & Christopher Chung & Ying Zhang & Danni Lin & Sherrina Patel & Fra, 2016. "Lens regeneration using endogenous stem cells with gain of visual function," Nature, Nature, vol. 531(7594), pages 323-328, March.
    2. Jose Ordovas-Montanes & Daniel F. Dwyer & Sarah K. Nyquist & Kathleen M. Buchheit & Marko Vukovic & Chaarushena Deb & Marc H. Wadsworth & Travis K. Hughes & Samuel W. Kazer & Eri Yoshimoto & Katherine, 2018. "Allergic inflammatory memory in human respiratory epithelial progenitor cells," Nature, Nature, vol. 560(7720), pages 649-654, August.
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    1. Liyue Li & Linyi Jiao & Danni Feng & Yizhang Yuan & Xiaoqian Yang & Jian Li & Dong Jiang & Hexin Chen & Qingxiang Meng & Ruchong Chen & Bixing Fang & Xuenong Zou & Zhenhua Luo & Xiaoyan Ye & Yue Hong , 2024. "Human apical-out nasal organoids reveal an essential role of matrix metalloproteinases in airway epithelial differentiation," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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