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

IF 44.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Science Pub Date : 2024-12-13 DOI:10.1126/science.ado5561

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

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引用次数: 0

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.

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Science 综合性期刊-综合性期刊

CiteScore

61.10

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0.90%

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审稿时长

2.1 months

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