中国科学院分子细胞科学卓越创新中心周斌小组发现，气道分泌细胞衍生的p63⁺祖细胞促进肺泡再生。这一研究成果于2024年9月3日在线发表在国际学术期刊《细胞—干细胞》上。

研究人员发现p63表达的祖细胞在博来霉素诱导的小鼠肺损伤后出现。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肺泡1型和2型细胞。双重重组酶介导的顺序遗传谱系追踪证明，p63⁺祖细胞源自气道分泌细胞，随后生成肺泡细胞。

从功能上看，p63的激活对于损伤后从分泌细胞有效再生肺泡至关重要。该研究确定了分泌细胞衍生的p63⁺祖细胞在肺泡修复中的作用，并提示其可能成为损伤后肺再生的潜在治疗途径。

据介绍，肺损伤会激活上皮干细胞或祖细胞进行肺泡修复和再生。揭示损伤诱导的祖细胞的起源和命运对阐明肺修复机制至关重要。

附：英文原文

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

Author: 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

Issue&Volume: September 3, 2024

Abstract: 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.

DOI: 10.1016/j.stem.2024.08.005

Source: https://www.cell.com/cell-stem-cell/abstract/S1934-5909(24)00291-1