ArticleThe Journal of clinical investigation2018
Expansion of hedgehog disrupts mesenchymal identity and induces emphysema phenotype.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
54 citing papers in PubMed, 86 citations in OpenAlex.
- A fibroblast-dependent TGF-β1/sFRP2 noncanonical Wnt signaling axis promotes epithelial metaplasia in idiopathic pulmonary fibrosis.The Journal of clinical investigation · 2024Trial
- Preclinical models of COPD: a state of the art review.The European respiratory journal · 2026Review
- Defective alveolar regeneration in emphysema: identifying dysfunctional cellular crosstalk and novel therapeutic opportunities for tissue repair.European respiratory review : an official journal of the European Respiratory Society · 2026Review
- Regenerative therapeutics for chronic obstructive pulmonary disease.Pharmacological reviews · 2026Review
- FGFR signaling establishes spatial gradients of secretory cell identities along the airway proximal-distal axis.Nature communications · 2026Article
- New approaches to uncover COPD pathobiology and develop therapies.JCI insight · 2026Review
- Developmental dynamics of bronchioalveolar stem cells revealed by dual-reporter lineage tracing.Respiratory research · 2026Article
- Hedgehog-interacting protein orchestrates alveologenesis and protects against bronchopulmonary dysplasia and emphysema.Science advances · 2025Article
- Heparan sulfate regulates myofibroblast heterogeneity and function to mediate niche homeostasis during alveolar morphogenesis.Nature communications · 2025Article
- Identification of Meibomian gland stem cell populations and mechanisms of aging.Nature communications · 2025Article
- Article
- Foxo3-mediated physiological cell competition ensures robust tissue patterning throughout vertebrate development.Nature communications · 2024Article
- Hedgehog Signaling Pathway in Fibrosis and Targeted Therapies.Biomolecules · 2024Review
- Identification of Meibomian gland stem cell populations and mechanisms of aging.bioRxiv : the preprint server for biology · 2024Article
- Breathing new life into the study of COPD with genes identified from genome-wide association studies.European respiratory review : an official journal of the European Respiratory Society · 2024Review
- Single-cell RNA sequencing to understand host-virus interactions.Virologica Sinica · 2024Review
- Progress and Gaps in Respiratory Disease Research and Treatment: Highlights of the IRM 2024 in Shanghai.Journal of respiratory biology and translational medicine · 2024Article
- Pulmonary inflammation and fibroblast immunoregulation: from bench to bedside.The Journal of clinical investigation · 2023Review
- Cellular and molecular mechanisms of Hedgehog signalling.Nature reviews. Molecular cell biology · 2023Review
- Unraveling the Distal Lung Destruction in Emphysema.American journal of respiratory and critical care medicine · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 5 institutions in 3 countries.
Funding
Abstract
GWAS have repeatedly mapped susceptibility loci for emphysema to genes that modify hedgehog signaling, but the functional relevance of hedgehog signaling to this morbid disease remains unclear. In the current study, we identified a broad population of mesenchymal cells in the adult murine lung receptive to hedgehog signaling, characterized by higher activation of hedgehog surrounding the proximal airway relative to the distal alveoli. Single-cell RNA-sequencing showed that the hedgehog-receptive mesenchyme is composed of mostly fibroblasts with distinct proximal and distal subsets with discrete identities. Ectopic hedgehog activation in the distal fibroblasts promoted expression of proximal fibroblast markers and loss of distal alveoli and airspace enlargement of over 20% compared with controls. We found that hedgehog suppressed mesenchymal-derived mitogens enriched in distal fibroblasts that regulate alveolar stem cell regeneration and airspace size. Finally, single-cell analysis of the human lung mesenchyme showed that segregated proximal-distal identity with preferential hedgehog activation in the proximal fibroblasts was conserved between mice and humans. In conclusion, we showed that differential hedgehog activation segregates mesenchymal identities of distinct fibroblast subsets and that disruption of fibroblast identity can alter the alveolar stem cell niche, leading to emphysematous changes in the murine lung.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.