Alveolar regeneration by airway secretory-cell-derived p63+ progenitors,Cell Stem Cell

当前位置： X-MOL 学术 › Cell Stem Cell › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Alveolar regeneration by airway secretory-cell-derived p63+ progenitors
Cell Stem Cell ( IF 19.8 ) Pub Date : 2024-09-03 , DOI: 10.1016/j.stem.2024.08.005
Zan Lv ₁ , Zixin Liu ₁ , Kuo Liu ₂ , Xiuyu Lin ₁ , Wenjuan Pu ₁ , Yan Li ₃ , Huan Zhao ₁ , Ying Xi ₄ , Pengfei Sui ₁ , Andrew E Vaughan ₅ , Astrid Gillich ₆ , Bin Zhou ₇

Affiliation

New Cornerstone Science Laboratory, Key Laboratory of Multi-Cell Systems, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.
Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China.
Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai, Shandong 264117, China; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China.
Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Calico Life Sciences LLC, South San Francisco, CA 94080, USA.
New Cornerstone Science Laboratory, Key Laboratory of Multi-Cell Systems, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China; Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China.

Lung injury activates epithelial stem or progenitor cells for alveolar repair and regeneration. Unraveling the origin and fate of injury-induced progenitors is crucial for elucidating lung repair mechanisms. Here, we report that p63-expressing progenitors emerge upon bleomycin-induced mouse lung injury. Single-cell RNA sequencing and clonal analysis reveal that these p63⁺ progenitors proliferate rapidly and differentiate into alveolar type 1 and type 2 cells through different trajectories. Dual recombinase-mediated sequential genetic-lineage tracing demonstrates that p63⁺ progenitors originate from airway secretory cells and subsequently generate alveolar cells. Functionally, p63 activation is essential for efficient alveolar regeneration from secretory cells post injury. Our study identifies secretory-cell-derived p63⁺ progenitors as contributors to alveolar repair, suggesting a potential therapeutic avenue for lung regeneration following injury.

中文翻译：

气道分泌细胞来源的 p63 + 祖细胞的肺泡再生

肺损伤会激活上皮干细胞或祖细胞进行肺泡修复和再生。揭示损伤诱导祖细胞的起源和命运对于阐明肺修复机制至关重要。在这里，我们报道了表达 p63 的祖细胞在博来霉素诱导的小鼠肺损伤中出现。单细胞 RNA 测序和克隆分析显示，这些 p63 ⁺ 祖细胞迅速增殖，并通过不同的轨迹分化为 1 型和 2 型肺泡细胞。双重组酶介导的序贯遗传谱系追踪表明，p63 ⁺ 祖细胞起源于气道分泌细胞，随后产生肺泡细胞。从功能上讲，p63 激活对于损伤后分泌细胞的高效肺泡再生至关重要。我们的研究确定分泌细胞来源的 p63 ⁺ 祖细胞是肺泡修复的贡献者，这表明损伤后肺再生的潜在治疗途径。

更新日期：2024-09-03

点击分享查看原文

点击收藏

公开下载

阅读更多本刊新发论文本刊介绍/投稿指南