研究人员表示，严重的肺损伤促使气道基底干细胞迁移并与肺泡干细胞竞争，导致发育不良修复。
研究人员发现这种“干细胞碰撞”产生了一个包含角蛋白5+上皮细胞，和可塑Pdgfra+间充质细胞的损伤诱导的组织生态位。单细胞分析表明，损伤诱导的生态位受间充质增殖和Notch信号的调控，Notch信号抑制了损伤生态位中的Wnt/Fgf信号。
相反，Notch信号的缺失会重新连接肺泡信号模式，从而促进功能再生和气体交换。损伤诱导小生境中的信号模式可以通过改变Wnt/Fgf信号传导方向，来区分纤维化和退行性人肺疾病。因此，该研究团队在肺中发现了一个损伤诱导的生态位，具有区分人类肺部疾病表型的能力。
附：英文原文
Title: An injury-induced mesenchymal-epithelial cell niche coordinates regenerative responses in the lung
Author: Dakota L. Jones, Michael P. Morley, Xinyuan Li, Yun Ying, Gan Zhao, Sarah E. Schaefer, Luis R. Rodriguez, Fabian L. Cardenas-Diaz, Shanru Li, Su Zhou, Ullas V. Chembazhi, Mijeong Kim, Chen Shen, Ana Nottingham, Susan M. Lin, Edward Cantu, Joshua M. Diamond, Maria C. Basil, Andrew E. Vaughan, Edward E. Morrisey
Issue&Volume: 2024-12-13
Abstract: Severe lung injury causes airway basal stem cells to migrate and outcompete alveolar stem cells, resulting in dysplastic repair. We found that this “stem cell collision” generates an injury-induced tissue niche containing keratin 5+ epithelial cells and plastic Pdgfra+ mesenchymal cells. Single-cell analysis revealed that the injury-induced niche is governed by mesenchymal proliferation and Notch signaling, which suppressed Wnt/Fgf signaling in the injured niche. Conversely, loss of Notch signaling rewired alveolar signaling patterns to promote functional regeneration and gas exchange. Signaling patterns in injury-induced niches can differentiate fibrotic from degenerative human lung diseases through altering the direction of Wnt/Fgf signaling. Thus, we have identified an injury-induced niche in the lung with the ability to discriminate human lung disease phenotypes.
DOI: ado5561
Source: https://www.science.org/doi/10.1126/science.ado5561