ArticlePloS one2015
Activation of NOTCH1 or NOTCH3 signaling skews human airway basal cell differentiation toward a secretory pathway.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
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.
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Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 citations in OpenAlex.
- Current strategies and opportunities to manufacture cells for modeling human lungs.Advanced drug delivery reviews · 2020Pooled it
- Spatial transcriptomics uncovers the hybrid molecular identity, ciliated phenotype, and immune signature of adenomyosis lesions.Science advances · 2026Article
- Extracellular vesicle-based delivery to airway basal cells for durable gene therapy in cystic fibrosis.Frontiers in bioengineering and biotechnology · 2026Review
- The mechanistic role of adipokine imbalance in airway inflammation, hyperresponsiveness, and remodeling in obesity-related asthma.Frontiers in endocrinology · 2026Review
- Article
- Closing the Gap: Use of Polidocanol to Study Human Airway Epithelial Repair.American journal of respiratory cell and molecular biology · 2025Article
- STAT3-Dependent Regulation of CFTR and Ciliogenesis Is Essential for Mucociliary Clearance and Innate Airway Defense in Hyper-IgE Syndrome.American journal of respiratory and critical care medicine · 2025Article
- Cholesterol Regulates Airway Epithelial Cell Differentiation by Inhibiting p53 Nuclear Translocation.International journal of molecular sciences · 2025Article
- HOXA1 Contributes to Bronchial Epithelial Cell Cycle Progression by Regulating p21/CDKN1A.International journal of molecular sciences · 2025Article
- The next frontier in lung development and regeneration research: harnessing iPSC models to illuminate notch signaling pathways.Frontiers in cell and developmental biology · 2025Review
- Article
- Identification of a Novel Subset of Human Airway Epithelial Basal Stem Cells.International journal of molecular sciences · 2024Article
- Sphingosine kinase 1-specific inhibitor PF543 reduces goblet cell metaplasia of bronchial epithelium in an acute asthma model.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- Proximal and Distal Bronchioles Contribute to the Pathogenesis of Non-Cystic Fibrosis Bronchiectasis.American journal of respiratory and critical care medicine · 2024Article
- Transcriptional Regulation of Airway Epithelial Cell Differentiation: Insights into the Notch Pathway and Beyond.International journal of molecular sciences · 2023Review
- Furin as a therapeutic target in cystic fibrosis airways disease.European respiratory review : an official journal of the European Respiratory Society · 2023Review
- Type 2 inflammation drives an airway basal stem cell program through insulin receptor substrate signaling.The Journal of allergy and clinical immunology · 2023Article
- Temporal Notch signaling regulates mucociliary cell fates through Hes-mediated competitive de-repression.bioRxiv : the preprint server for biology · 2023Article
- TMEM16A/F support exocytosis but do not inhibit Notch-mediated goblet cell metaplasia of BCi-NS1.1 human airway epithelium.Frontiers in physiology · 2023Article
- 3D tissue-engineered lung models to study immune responses following viral infections of the small airways.Stem cell research & therapy · 2022Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Airway basal cells (BC) function as stem/progenitor cells capable of differentiating into the luminal ciliated and secretory cells to replenish the airway epithelium during physiological turnover and repair. The objective of this study was to define the role of Notch signaling in regulating human airway BC differentiation into a pseudostratified mucociliated epithelium. Notch inhibition with γ-secretase inhibitors demonstrated Notch activation is essential for BC differentiation into secretory and ciliated cells, but more so for the secretory lineage. Sustained cell autonomous ligand independent Notch activation via lentivirus expression of the intracellular domain of each Notch receptor (NICD1-4) demonstrated that the NOTCH2 and 4 pathways have little effect on BC differentiation into secretory and ciliated cells, while activation of the NOTCH1 or 3 pathways has a major influence, with persistent expression of NICD1 or 3 resulting in a skewing toward secretory cell differentiation with a parallel decrease in ciliated cell differentiation. These observations provide insights into the control of the balance of BC differentiation into the secretory vs ciliated cell lineage, a balance that is critical for maintaining the normal function of the airway epithelium in barrier defense against the inhaled environment.
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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.