Journal article
An injury-induced mesenchymal-epithelial cell niche coordinates regenerative responses in the lung
Science (American Association for the Advancement of Science), Vol.386(6727), p.eado5561
12/13/2024
DOI: 10.1126/science.ado5561
PMCID: PMC13159043
PMID: 39666855
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.
Details
- Title: Subtitle
- An injury-induced mesenchymal-epithelial cell niche coordinates regenerative responses in the lung
- Creators
- Dakota L Jones - University of PennsylvaniaMichael P Morley - University of PennsylvaniaXinyuan Li - University of PennsylvaniaYun Ying - University of PennsylvaniaGan Zhao - University of PennsylvaniaSarah E Schaefer - University of PennsylvaniaLuis R Rodriguez - University of PennsylvaniaFabian L Cardenas-Diaz - University of PennsylvaniaShanru Li - University of PennsylvaniaSu Zhou - University of PennsylvaniaUllas V Chembazhi - University of PennsylvaniaMijeong Kim - University of PennsylvaniaChen Shen - University of PennsylvaniaAna Nottingham - University of PennsylvaniaSusan M Lin - University of PennsylvaniaEdward Cantu - University of PennsylvaniaJoshua M Diamond - University of PennsylvaniaMaria C Basil - University of PennsylvaniaAndrew E Vaughan - University of PennsylvaniaEdward E Morrisey - University of Pennsylvania
- Resource Type
- Journal article
- Publication Details
- Science (American Association for the Advancement of Science), Vol.386(6727), p.eado5561
- DOI
- 10.1126/science.ado5561
- PMID
- 39666855
- PMCID
- PMC13159043
- NLM abbreviation
- Science
- ISSN
- 0036-8075
- eISSN
- 1095-9203
- Grant note
- R01 HL153539 / NHLBI NIH HHS L30 HL165571 / NHLBI NIH HHS R01 HL162683 / NHLBI NIH HHS R01 HL168803 / NHLBI NIH HHS K99 HL173656 / NHLBI NIH HHS U01 HL148857 / NHLBI NIH HHS R01 HL155821 / NHLBI NIH HHS K08 HL163398 / NHLBI NIH HHS R01 HL152194 / NHLBI NIH HHS R01 HL164929 / NHLBI NIH HHS
- Language
- English
- Date published
- 12/13/2024
- Academic Unit
- Anatomy and Cell Biology
- Record Identifier
- 9984949262402771
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