ArticleDisease models & mechanisms2023
Fibroblast-derived EGF ligand neuregulin 1 induces fetal-like reprogramming of the intestinal epithelium without supporting tumorigenic growth.
Article in Disease models & mechanisms, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- Proliferation and differentiation in intestinal organoids are balanced by ligand-modulated EGFR trafficking.Life science alliance · 2026Article
- Helicobacter pylori triggers gastric mucosal remodeling toward a fetal-like transcriptional program via stromal IL-1β signaling.Nature communications · 2026Article
- Building and regenerating intestines by manipulating intestinal stem cells.Nature reviews. Gastroenterology & hepatology · 2026Review
- Single-cell RNA sequencing of hematopoietic and non-hematopoietic cells defines a distinct signature in atopic and NRG1 mouse lung.Scientific reports · 2026Article
- Myosin VB is critical for progenitor cell identity and function in the intestine.Stem cell reports · 2026Article
- Observational
- Defining the mucosal ecosystem: epithelial-mesenchymal interdependence in gastrointestinal health and disease.Nature reviews. Gastroenterology & hepatology · 2025Review
- Harnessing 3D models to uncover the mechanisms driving infectious and inflammatory disease in the intestine.BMC biology · 2024Review
- An extragenital cell population contributes to urethra closure during mouse penis development.Science advances · 2024Article
- Single-cell resolution of intestinal regeneration in pythons without crypts illuminates conserved vertebrate regenerative mechanisms.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Neuregulin 1 (NRG1) and its receptors in the enteric nervous system and other parts of the gastrointestinal wall.Histology and histopathology · 2024Review
- Activation of fetal-like molecular programs during regeneration in the intestine and beyond.Cell stem cell · 2024Review
- E2F transcription factors promote tumorigenicity in pancreatic ductal adenocarcinoma.Cancer medicine · 2024Article
- An extra-genital cell population contributes to urethra closure during mouse penis development.bioRxiv : the preprint server for biology · 2023Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 3 countries.
Funding
Abstract
Growth factors secreted by stromal fibroblasts regulate the intestinal epithelium. Stroma-derived epidermal growth factor (EGF) family ligands are implicated in epithelial regeneration and tumorigenesis, but their specific contributions and associated mechanisms remain unclear. Here, we use primary intestinal organoids modeling homeostatic, injured and tumorigenic epithelia to assess how the fibroblast-derived EGF family ligands neuregulin 1 (NRG1) and epiregulin (EREG) regulate the intestinal epithelium. NRG1 was expressed exclusively in the stroma, robustly increased crypt budding and protected intestinal epithelial organoids from radiation-induced damage. NRG1 also induced regenerative features in the epithelium, including a fetal-like transcriptome, suppression of the Lgr5+ stem cell pool and remodeling of the epithelial actin cytoskeleton. Intriguingly, unlike EGF and EREG, NRG1 failed to support the growth of pre-tumorigenic intestinal organoids lacking the tumor suppressor Apc, commonly mutated in human colorectal cancer (CRC). Interestingly, high expression of stromal NRG1 was associated with improved survival in CRC cohorts, suggesting a tumor-suppressive function. Our results highlight the power of stromal NRG1 in transcriptional reprogramming and protection of the intestinal epithelium from radiation injury without promoting tumorigenesis.
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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.