The State Key Laboratory of Cell Biology, CAS Center for Excellence on Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Institute of Nutritional Sciences, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Nat Genet. 2019 Apr;51(4):728-738. doi: 10.1038/s41588-019-0346-6. Epub 2019 Feb 18.
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.
鉴定负责肺部修复和再生的干细胞对于肺部疾病的治疗很重要。最近，有人提出位于支气管肺泡-导管交界处的独特细胞群可能包含肺再生的内源性干细胞。然而，支气管肺泡干细胞（BASCs）在体内的作用仍存在争议，并且这些细胞对肺再生的贡献尚不清楚。在这里，我们生成了一种遗传谱系追踪系统，该系统使用双重组酶（Cre 和 Dre）在体内特异性地追踪 BASCs。命运图谱和克隆分析表明，BASCs 被激活，并对不同的肺部损伤有明显的反应，并分化为多种细胞谱系，包括 club 细胞、纤毛细胞以及肺泡 1 型和 2 型细胞，以进行肺再生。这项研究提供了体内遗传证据，表明 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。
