Lung regeneration by multipotent stem cells residing at the bronchioalveolar-duct junction
Lung regeneration by multipotent stem cells residing at the bronchioalveolar-duct junction
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位于细支气管肺泡管交界处的多能干细胞实现肺再生
DOI：
10.1038/s41588-019-0346-6
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发表时间：
2019-04-01
期刊：
影响因子：
30.8
通讯作者：
Zhou, Bin
中科院分区：
文献类型：
--
作者：
Liu, Qiaozhen;Liu, Kuo;Zhou, Bin
表征负责肺修复和再生的干细胞对于肺部疾病的治疗是重要的。最近，一个独特的细胞群位于支气管肺泡管交界处已被提出包含内源性干细胞的肺再生。然而，支气管肺泡干细胞（BASCs）在体内的作用仍然存在争议，这些细胞对肺再生的贡献尚不清楚。在这里，我们产生了一个遗传谱系追踪系统，该系统使用双重组酶（Cre和Dre）在体内特异性追踪BASCs。命运图和克隆分析表明，BASC被激活并对不同的肺损伤有明显的反应，并分化成多种细胞谱系，包括俱乐部细胞、纤毛细胞以及用于肺再生的肺泡1型和2型细胞。这项研究提供了体内遗传学证据，证明BASCs是真正的肺上皮干细胞，在肺修复和再生过程中具有多能性和自我更新能力。
Characterizing the stem cells responsible for lung repair and regeneration is important for the treatment of pulmonary diseases. Recently, a unique cell population located at the bronchioalveolar-duct junctions has been proposed to comprise endogenous stem cells for lung regeneration. However, the role of bronchioalveolar stem cells (BASCs) in vivo remains debated, and the contribution of such cells to lung regeneration is not known. Here we generated a genetic lineage-tracing system that uses dual recombinases (Cre and Dre) to specifically track BASCs in vivo. Fate-mapping and clonal analysis showed that BASCs became activated and responded distinctly to different lung injuries, and differentiated into multiple cell lineages including club cells, ciliated cells, and alveolar type 1 and type 2 cells for lung regeneration. This study provides in vivo genetic evidence that BASCs are bona fide lung epithelial stem cells with deployment of multipotency and self-renewal during lung repair and regeneration.