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

Author:

Hong YueORCID,Shan Shan,Gu Ye,Huang Haidong,Zhang Quncheng,Han Yang,Dong YongpinORCID,Liu Zeyu,Huang Moli,Ren TaoORCID

Abstract

AbstractUnderstanding 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.

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary

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