Preprint
An injury-induced tissue niche shaped by mesenchymal plasticity coordinates the regenerative and disease response in the lung
bioRxiv
Cold Spring Harbor Laboratory, 1.1
02/29/2024
DOI: 10.1101/2024.02.26.582147
PMCID: PMC10962740
PMID: 38529490
Abstract
Severe lung injury causes basal stem cells to migrate and outcompete alveolar stem cells resulting in dysplastic repair and a loss of gas exchange function. This “stem cell collision” is part of a multistep process that is now revealed to generate an injury-induced tissue niche (iTCH) containing Keratin 5+ epithelial cells and plastic Pdgfra+ mesenchymal cells. Temporal and spatial single cell analysis reveals that iTCHs are governed by mesenchymal proliferation and Notch signaling, which suppresses Wnt and Fgf signaling in iTCHs. Conversely, loss of Notch in iTCHs rewires alveolar signaling patterns to promote euplastic regeneration and gas exchange. The signaling patterns of iTCHs can differentially phenotype fibrotic from degenerative human lung diseases, through apposing flows of FGF and WNT signaling. These data reveal the emergence of an injury and disease associated iTCH in the lung and the ability of using iTCH specific signaling patterns to discriminate human lung disease phenotypes.
Details
- Title: Subtitle
- An injury-induced tissue niche shaped by mesenchymal plasticity coordinates the regenerative and disease response in the lung
- Creators
- Dakota L. Jones - University of PennsylvaniaMichael P. Morley - University of PennsylvaniaXinyuan Li - University of PennsylvaniaYun Ying - University of PennsylvaniaFabian L. Cardenas-Diaz - University of PennsylvaniaShanru Li - University of PennsylvaniaSu Zhou - University of PennsylvaniaSarah E. Schaefer - University of PennsylvaniaUllas V. Chembazhi - University of PennsylvaniaAna Nottingham - University of PennsylvaniaSusan 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
- Preprint
- Publication Details
- bioRxiv
- Edition
- 1.1
- DOI
- 10.1101/2024.02.26.582147
- PMID
- 38529490
- PMCID
- PMC10962740
- NLM abbreviation
- bioRxiv
- ISSN
- 2692-8205
- eISSN
- 2692-8205
- Publisher
- Cold Spring Harbor Laboratory
- Number of pages
- 54
- Language
- English
- Date posted
- 02/29/2024
- Academic Unit
- Anatomy and Cell Biology
- Record Identifier
- 9984958644302771
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