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.

中文翻译：

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损伤诱导的间充质-上皮细胞生态位协调肺中的再生反应


严重的肺损伤会导致气道基底干细胞迁移并超过肺泡干细胞，从而导致发育不良修复。我们发现这种“干细胞碰撞”产生了一个损伤诱导的组织生态位，其中包含角蛋白 5 + 上皮细胞和塑料 Pdgfra + 间充质细胞。单细胞分析显示，损伤诱导的生态位受间充质增殖和 Notch 信号传导控制，这抑制了受伤生态位中的 Wnt/Fgf 信号传导。相反，Notch 信号的缺失会重新连接肺泡信号传导模式，以促进功能再生和气体交换。损伤诱导的生态位中的信号传导模式可以通过改变 Wnt/Fgf 信号传导的方向来区分纤维化和退行性人类肺部疾病。因此，我们已经确定了肺部损伤诱导的生态位，具有区分人类肺部疾病表型的能力。