Malfunction of airway basal stem cells plays a crucial role in pathophysiology of tracheobronchopathia osteoplastica.
Malfunction of airway basal stem cells plays a crucial role in pathophysiology of tracheobronchopathia osteoplastica.
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气道基底干细胞功能障碍在骨塑性气管支气管病的病理生理学中起着至关重要的作用
DOI：
10.1038/s41467-022-28903-7
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发表时间：
2022-03-14
影响因子：
16.6
通讯作者：
Ren T
中科院分区：
文献类型：
--
作者：
Hong Y;Shan S;Gu Y;Huang H;Zhang Q;Han Y;Dong Y;Liu Z;Huang M;Ren T
了解疾病相关的干细胞异常对预防和治疗人类疾病以及再生医学具有重要的临床意义。在这里，我们报告了一个多方面的研究气道上皮干细胞在气管支气管病变骨软骨（TO），未被发现的气管支气管疾病的病因不明，缺乏具体的治疗。上皮鳞状上皮化生和异位骨形成伴异常软骨增殖和钙沉积是这种疾病的关键病理标志，但尚不清楚它们是否同时发生或共享某些共同的致病机制。通过在转录和表观遗传水平上的功能评估和全基因组分析，我们揭示了气道基底细胞通过充当炎症和TGFβ-BMP信号的储存库在TO进展中的作用，其通过细胞外信号传导和基质重塑促进上皮化生和间充质骨软骨形成。通过细胞校正或局部通路干预恢复微环境可能提供治疗益处。气管支气管病变是一种少见的以气管和支气管鳞状上皮化生和异位骨形成为特征的疾病。在这里，作者应用功能，以及全基因组转录和表观遗传分析，以确定气道基底细胞功能障碍的基础TO。
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. Tracheobronchopathia osteoplastica (TO), is an underreported affliction characterized by squamous metaplasia and heterotopic bone formation in trachea and bronchi. Here the authors apply functional, as well as genome-wide transcriptional and epigenetic profiling to identify airway basal cells dysfunction underlying TO.
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影响因子：
6.2
作者：
Duque, Gustavo;Huang, Dao Chao;Kremer, Richard
通讯作者：
Kremer, Richard
影响因子：
4.8
作者：
Faria, Alessandra V. de S.;Akyala, Adamu Ishaku;Peppelenbosch, Maikel P.
通讯作者：
Peppelenbosch, Maikel P.
影响因子：
6
作者：
Chien, Szu-Yu;Tsai, Chun-Hao;Tang, Chih-Hsin
通讯作者：
Tang, Chih-Hsin
DOI：
10.1165/rcmb.2013-0049oc
发表时间：
2013-12-01
影响因子：
6.4
作者：
Ghosh, Moumita;Ahmad, Shama;Reynolds, Susan D.
通讯作者：
Reynolds, Susan D.
DOI：
10.1165/rcmb.2016-0181ma
发表时间：
2017-01-01
影响因子：
6.4
作者：
Ghosh, Moumita;Ahmad, Shama;Reynolds, Susan D.
通讯作者：
Reynolds, Susan D.