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Local lung hypoxia determines epithelial fate decisions during alveolar regeneration | |
2017 | |
发表期刊 | NATURE CELL BIOLOGY |
ISSN | 1465-7392 |
EISSN | 1476-4679 |
卷号 | 19期号:8页码:904-14 |
发表状态 | 已发表 |
DOI | 10.1038/ncb3580 |
摘要 | After influenza infection, lineage-negative epithelial progenitors (LNEPs) exhibit a binary response to reconstitute epithelial barriers: activating a Notch-dependent Delta Np63/cytokeratin 5 (Krt5) remodelling program or differentiating into alveolar type II cells (AEC2s). Here we show that local lung hypoxia, through hypoxia-inducible factor (HIF1 alpha), drives Notch signalling and Krt5(pos) basal-like cell expansion. Single-cell transcriptional profiling of human AEC2s from fibrotic lungs revealed a hypoxic subpopulation with activated Notch, suppressed surfactant protein C (SPC), and transdifferentiation toward a Krt5(pos) basal-like state. Activated murine Krt5(pos) LNEPs and diseased human AEC2s upregulate strikingly similar core pathways underlying migration and squamous metaplasia. While robust, HIF1 alpha-driven metaplasia is ultimately inferior to AEC2 reconstitution in restoring normal lung function. HIF1 alpha deletion or enhanced Wnt/beta-catenin activity in Sox2(pos) LNEPs blocks Notch and Krt5 activation, instead promoting rapid AEC2 differentiation and migration and improving the quality of alveolar repair. |
URL | 查看原文 |
收录类别 | SCI |
语种 | 英语 |
WOS研究方向 | Cell Biology |
WOS类目 | Cell Biology |
WOS记录号 | WOS:000406500300008 |
WOS关键词 | AIRWAY STEM-CELLS ; PROGENITOR CELLS ; BETA-CATENIN ; INDUCIBLE FACTOR-1-ALPHA ; PULMONARY-FIBROSIS ; BREAST-CANCER ; ADULT LUNG ; IN-VIVO ; NOTCH ; MICE |
原始文献类型 | Article |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/119974 |
专题 | 个人在本单位外知识产出 |
通讯作者 | Chapman, Harold A. |
作者单位 | 1.UCSF, Cardiovasc Res Inst, Dept Med, San Francisco, CA 94143 USA 2.UCSF, Dept Anat, San Francisco, CA 94143 USA 3.Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA 4.Cincinnati Childrens Hosp Med Ctr, Div Pulm Biol, Cincinnati, OH 45229 USA 5.Univ Penn, Inst Regenerat Med, Philadelphia, PA 19104 USA 6.Genentech Inc, Dept Immunol, San Francisco, CA 94080 USA 7.Univ Penn, Dept Biomed Sci, Sch Vet Med, Philadelphia, PA 19104 USA |
推荐引用方式 GB/T 7714 | Xi, Ying,Kim, Thomas,Brumwell, Alexis N.,et al. Local lung hypoxia determines epithelial fate decisions during alveolar regeneration[J]. NATURE CELL BIOLOGY,2017,19(8):904-14. |
APA | Xi, Ying.,Kim, Thomas.,Brumwell, Alexis N..,Driver, Ian H..,Wei, Ying.,...&Vaughan, Andrew E..(2017).Local lung hypoxia determines epithelial fate decisions during alveolar regeneration.NATURE CELL BIOLOGY,19(8),904-14. |
MLA | Xi, Ying,et al."Local lung hypoxia determines epithelial fate decisions during alveolar regeneration".NATURE CELL BIOLOGY 19.8(2017):904-14. |
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