ArticleThe Journal of clinical investigation2009
SPDEF is required for mouse pulmonary goblet cell differentiation and regulates a network of genes associated with mucus production.
Article in The Journal of clinical investigation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 268 papers.
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Who cites it
268 citing papers in PubMed, 400 citations in OpenAlex.
- Trial
- Article
- Invasive mucinous adenocarcinoma of the lung: integrating molecular landscape, imaging phenotypes, and translational therapeutic strategies.Translational lung cancer research · 2026Review
- Pseudomonas aeruginosa-derived volatile organic compounds modulate AhR signaling to dysregulate airway mucus homeostasis.Nature communications · 2026Article
- The RNA-binding protein Imp1 promotes a Spdef transcriptional program and mucus fucosylation during necrotizing enterocolitis.American journal of physiology. Gastrointestinal and liver physiology · 2026Article
- Hypomethylation of FAM83A in lung adenocarcinoma mirrors an epigenetic signature of airway cell differentiation states.Discover oncology · 2026Article
- Th2 cytokine-induced mucociliary remodeling in chronic rhinosinusitis: implications for antiviral defense and epithelial function.Respiratory research · 2026Article
- Epithelial cells in chronic obstructive pulmonary disease exacerbations: Targets for lung repair.Pharmacological reviews · 2026Review
- KCNJ2 is Required for NLRP3 Inflammasome Activation That Drives Allergic Airway Inflammation and Remodeling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A Mouthful of Genomic Data: Single-Cell Insights into Salivary Gland Biology and Disease.Biology · 2026Review
- Butyrate SilencesAllergy, asthma & immunology research · 2026Article
- The RNA-binding protein Imp1 promotes a Spdef transcriptional program and mucus fucosylation during necrotizing enterocolitis.bioRxiv : the preprint server for biology · 2026Article
- The FOXA transcription factors in allergic airway disease and asthma.Frontiers in allergy · 2026Review
- Orchestrating immunopathology: the spectrum of programmed cell death pathways co-opted by influenza a virus in pulmonary immunity.Frontiers in immunology · 2026Review
- Repurposing approved drugs as Pendrin (Frontiers in pharmacology · 2026Article
- Semaglutide and pioglitazone restore airway mucosal homeostasis by resolvingFrontiers in immunology · 2026Article
- Article
- Mutant GNAS drives a pyloric metaplasia with tumor suppressive glycans in intraductal papillary mucinous neoplasia.Cell reports · 2025Article
- Specialized gas-exchange endothelium of the zebrafish gill.bioRxiv : the preprint server for biology · 2025Article
- Rhinovirus C15 infection induces airway epithelial cell remodeling and robust inflammatory responses: Potential implications for airway obstruction in children.Mucosal immunology · 2025Article
208 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Various acute and chronic inflammatory stimuli increase the number and activity of pulmonary mucus-producing goblet cells, and goblet cell hyperplasia and excess mucus production are central to the pathogenesis of chronic pulmonary diseases. However, little is known about the transcriptional programs that regulate goblet cell differentiation. Here, we show that SAM-pointed domain-containing Ets-like factor (SPDEF) controls a transcriptional program critical for pulmonary goblet cell differentiation in mice. Initial cell-lineage-tracing analysis identified nonciliated secretory epithelial cells, known as Clara cells, as the progenitors of goblet cells induced by pulmonary allergen exposure in vivo. Furthermore, in vivo expression of SPDEF in Clara cells caused rapid and reversible goblet cell differentiation in the absence of cell proliferation. This was associated with enhanced expression of genes regulating goblet cell differentiation and protein glycosylation, including forkhead box A3 (Foxa3), anterior gradient 2 (Agr2), and glucosaminyl (N-acetyl) transferase 3, mucin type (Gcnt3). Consistent with these findings, levels of SPDEF and FOXA3 were increased in mouse goblet cells after sensitization with pulmonary allergen, and the proteins were colocalized in goblet cells lining the airways of patients with chronic lung diseases. Deletion of the mouse Spdef gene resulted in the absence of goblet cells in tracheal/laryngeal submucosal glands and in the conducting airway epithelium after pulmonary allergen exposure in vivo. These data show that SPDEF plays a critical role in regulating a transcriptional network mediating the goblet cell differentiation and mucus hyperproduction associated with chronic pulmonary disorders.
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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.