Alveolar regeneration by airway secretory-cell-derived p63+ progenitors
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<sup>+</sup> 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<sup>+</sup> 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<sup>+</sup> progenitors as contributors to alveolar repair, suggesting a potential therapeutic avenue for lung regeneration following injury.
Authors
- Wenjuan Pu (ORCID: https://orcid.org/0000-0001-5155-5178)
- Andrew E. Vaughan (ORCID: https://orcid.org/0000-0001-5740-643X)
- Pengfei Sui (ORCID: https://orcid.org/0000-0002-8140-7050)
- Zan Lv (ORCID: https://orcid.org/0000-0001-9743-4419)
- Astrid Gillich (ORCID: https://orcid.org/0000-0002-7016-0494)
- Ying Xi (ORCID: https://orcid.org/0000-0002-1796-3538)
- Yan Li (ORCID: https://orcid.org/0000-0002-3468-9235)
- Kuo Liu (ORCID: https://orcid.org/0000-0003-0757-7833)
- Bin Zhou (ORCID: https://orcid.org/0000-0001-5278-5522)
- Huan Zhao
- Zixin Liu (ORCID: https://orcid.org/0000-0003-2321-8929)
- Xiuyu Lin
Institutions
- Chinese Academy of Sciences (CN)
- ShanghaiTech University (CN)
- Shanghai Institute of Materia Medica (CN)
- Center for Excellence in Molecular Cell Science (CN)
- University of Chinese Academy of Sciences (CN)
- University of Pennsylvania (US)
Publication Details
- Journal
- Cell stem cell
- Published
- 2024-09-03
- DOI
- https://doi.org/10.1016/j.stem.2024.08.005
- Citations
- 29
- Primary Topic
- Neonatal Respiratory Health Research
- Type
- article
- Field-Weighted Citation Impact
- 12.15
Funders
- National Natural Science Foundation of China
- National Key Research and Development Program of China Stem Cell and Translational Research