Alveolar regeneration by airway secretory-cell-derived p63+ progenitors

作者：Zan Lv, Zixin Liu, Kuo Liu, Xiuyu Lin, Wenjuan Pu, Yan Li, Huan Zhao, Ying Xi, Pengfei Sui, Andrew E. Vaughan, Astrid Gillich, Bin Zhou · 发表于：Cell stem cell · 年份：2024 · DOI：10.1016/j.stem.2024.08.005 · 被引用次数：40 · 研究领域：Neonatal Respiratory Health Research、Congenital Diaphragmatic Hernia Studies、Tracheal and airway disorders

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.