当前位置: X-MOL 学术Cell Stem Cell › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Distinct Airway Epithelial Stem Cells Hide among Club Cells but Mobilize to Promote Alveolar Regeneration.
Cell Stem Cell ( IF 19.8 ) Pub Date : 2020-01-23 , DOI: 10.1016/j.stem.2019.12.014
Jaymin J Kathiriya 1 , Alexis N Brumwell 1 , Julia R Jackson 1 , Xiaodan Tang 2 , Harold A Chapman 1
Affiliation  

Lung injury activates specialized adult epithelial progenitors to regenerate the epithelium. Depending on the extent of injury, both remaining alveolar type II cells (AEC2s) and distal airway stem/progenitors mobilize to cover denuded alveoli and restore normal barriers. The major source of airway stem/progenitors other than basal-like cells remains uncertain. Here, we define a distinct subpopulation (∼5%) of club-like lineage-negative epithelial progenitors (LNEPs) marked by high H2-K1 expression critical for alveolar repair. Quiescent H2-K1high cells account for virtually all in vitro regenerative activity of airway lineages. After bleomycin injury, H2-K1 cells expand and differentiate in vivo to alveolar lineages. However, injured H2-K1 cells eventually develop impaired self-renewal with features of senescence, limiting complete repair. Normal H2-K1high cells transplanted into injured lungs differentiate into alveolar cells and rescue lung function. These findings indicate that small subpopulations of specialized stem/progenitors are required for effective lung regeneration and are a potential therapeutic adjunct after major lung injury.

中文翻译:

不同的气道上皮干细胞藏在俱乐部细胞中,但可动员以促进肺泡再生。

肺损伤激活了专门的成年上皮祖细胞以再生上皮。根据损伤程度,剩余的II型肺泡细胞(AEC2s)和远端气道干/祖细胞动员起来以覆盖裸露的肺泡并​​恢复正常屏障。除基底样细胞外,气道干/祖细胞的主要来源仍不确定。在这里,我们定义了以肺泡修复至关重要的高H2-K1表达为标志的俱乐部样谱系阴性上皮祖细胞(LNEPs)的不同亚群(〜5%)。静止的H2-K1high细胞几乎占了气道谱系的所有体外再生活性。博来霉素损伤后,H2-K1细胞在体内扩增并分化为肺泡谱系。然而,受损的H2-K1细胞最终会发展出衰老的自我更新功能,从而限制了其完全修复。移植到受伤肺中的正常H2-K1high细胞分化为肺泡细胞并拯救肺功能。这些发现表明,特殊的茎/祖细胞的小亚群是有效的肺再生所必需的,并且是重大肺损伤后的潜在治疗辅助剂。
更新日期:2020-01-24
down
wechat
bug