期刊
NATURE GENETICS
卷 51, 期 4, 页码 728-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41588-019-0346-6
关键词
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资金
- Strategic Priority Research Program of the Chinese Academy of Sciences (CAS) [XDB19000000, XDA16020204, XDA16020404, XDA16020501]
- National Science Foundation of China [31730112, 91639302, 31625019, 91849202, 81761138040, 31601168, 31701292, 81872241, 31571503, 91749122, 81872132, 81430066, 31621003]
- National Key Research and Development Program of China [2018YFA0107900, 2016YFC1300600, 2018YFA0108100, 2017YFC1001303, 2017YFA0505500]
- Key Project of Frontier Sciences of CAS [QYZDB-SSW-SMC003]
- Shanghai Science and Technology Commission [17ZR1449600, 17ZR1449800, 15XD1504000]
- Shanghai Yangfan Project [16YF1413400]
- China Postdoctoral Innovative Talent Support Program [BX20180338]
- China Young Talents Lift Engineering [YESS20160050, 2017QNRC001]
- Research Beyond Borders at Boehringer Ingelheim Pharma GmbH
- Astrazeneca
- Royal Society-Newton Advanced Fellowship [NA170109]
- Program for Guangdong Introducing Innovative and Entrepreneurial Teams [2017ZT07S347]
- Genome Tagging Project (GTP) Center
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.
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