ArticleCells2021
The NOTCH3 Downstream Target HEYL Is Required for Efficient Human Airway Basal Cell Differentiation.
Article in Cells, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 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.
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Who cites it
8 citing papers in PubMed, 10 citations in OpenAlex.
- Resolving thyroid lineage cell trajectories merging into a dual endocrine gland in mammals.Nature communications · 2026Article
- A Notch signal pathway related gene signature predicts overall survival in colorectal cancer.BMC gastroenterology · 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
- Single-cell transcriptomics reveals e-cigarette vapor-induced airway epithelial remodeling and injury.Respiratory research · 2024Article
- Identification of cancer risk assessment signature in patients with chronic obstructive pulmonary disease and exploration of the potential key genes.Annals of medicine · 2022Article
- The emerging role of NOTCH3 receptor signalling in human lung diseases.Expert reviews in molecular medicine · 2022Review
- Partial-Methylated HeyL Promoter Predicts the Severe Illness in Egyptian COVID-19 Patients.Disease markers · 2022Article
- Roles of transducin-like enhancer of split (TLE) family proteins in tumorigenesis and immune regulation.Frontiers in cell and developmental biology · 2022Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Basal cells (BCs) are stem/progenitor cells of the mucociliary airway epithelium, and their differentiation is orchestrated by the NOTCH signaling pathway. NOTCH3 receptor signaling regulates BC to club cell differentiation; however, the downstream responses that regulate this process are unknown. Overexpression of the active NOTCH3 intracellular domain (NICD3) in primary human bronchial epithelial cells (HBECs) on in vitro air-liquid interface culture promoted club cell differentiation. Bulk RNA-seq analysis identified 692 NICD3-responsive genes, including the classical NOTCH target HEYL, which increased in response to NICD3 and positively correlated with SCGB1A1 (club cell marker) expression. siRNA knockdown of HEYL decreased tight junction formation and cell proliferation. Further, HEYL knockdown reduced club, goblet and ciliated cell differentiation. In addition, we observed decreased expression of HEYL in HBECs from donors with chronic obstructive pulmonary disease (COPD) vs. normal donors which correlates with the impaired differentiation capacity of COPD cells. Finally, overexpression of HEYL in COPD HBECs promoted differentiation into club, goblet and ciliated cells, suggesting the impaired capacity of COPD cells to generate a normal airway epithelium is a reversible phenotype that can be regulated by HEYL. Overall, our data identify the NOTCH3 downstream target HEYL as a key regulator of airway epithelial differentiation.
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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.