近日，美国加州大学旧金山分校Harold A. Chapman及其研究团队发现，截然不同的呼吸道道上皮干细胞隐藏在棒状细胞中，但能够促进肺泡再生。相关论文2020年1月23日在线发表在《细胞—干细胞》上。

研究人员定义了一群对肺泡修复至关重要的棒状细胞样谱系阴性的上皮祖细胞（LNEP）亚群（约5%），并以H2-K1高表达为标志。静息的H2-K1高表达细胞几乎含有呼吸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细胞最终会导致自我更新能力的受损并带有衰老特征，从而限制了其完全修复。移植到受伤肺中的正常H2-K1高表达细胞分化为肺泡细胞并拯救肺功能。这些发现表明，专门的干/祖细胞亚群是有效肺部再生所需的，并且是严重肺部损伤后的潜在治疗手段。

据了解，肺损伤激活了专职的成年上皮祖细胞来再生上皮。根据损伤程度，剩余的II型肺泡细胞（AEC2）和远端呼吸道干/祖细胞会被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，呼吸道道干/祖细胞的主要来源仍不确定。

附：英文原文

Title: Distinct Airway Epithelial Stem Cells Hide among Club Cells but Mobilize to Promote Alveolar Regeneration

Author: Jaymin J. Kathiriya, Alexis N. Brumwell, Julia R. Jackson, Xiaodan Tang, Harold A. Chapman

Issue&Volume: January 23, 2020

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

DOI: 10.1016/j.stem.2019.12.014

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(19)30572-7