An injury-induced mesenchymal-epithelial cell niche coordinates regenerative responses in the lung

• 成果类型: Article
• 署名作者: Jones, Dakota L.; Morley, Michael P.; Li, Xinyuan; Ying, Yun; Zhao, Gan; Schaefer, Sarah E.; Rodriguez, Luis R.; Cardenas-Diaz, Fabian L.; Li, Shanru; Zhou, Su; Chembazhi, Ullas V.; Kim, Mijeong; Shen, Chen; Nottingham, Ana; Lin, Susan M.; Cantu, Edward; Diamond, Joshua M.; Basil, Maria C.; Vaughan, Andrew E.; Morrisey, Edward E.
• 署名单位: University of Pennsylvania; University of Pennsylvania; University of Pennsylvania; University of Pennsylvania; University of Pennsylvania; University of Pennsylvania
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-9942
• DOI: 10.1126/science.ado5561
• 发表日期: 2024-12-13
• 关键词: stem-cells; r package; repair; progenitors; homeostasis; lineage

摘要

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.