ArticleGastroenterology2012
Redundant sources of Wnt regulate intestinal stem cells and promote formation of Paneth cells.
Article in Gastroenterology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 391 papers, 1 of them a synthesis that pooled it.
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Who cites it
391 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Paneth Cells: Recent Updates on Elucidating Therapeutic Implications in Gastroenterological Disease Management.Current medicinal chemistry · 2025Pooled it
- Updated Protocols for 3D and 2D Culture and Histological Analysis of Intestinal Organoids.Methods in molecular biology (Clifton, N.J.) · 2027Article
- Review
- Paneth cell-derived Notch ligands DLL1 and DLL4 are crucial for intestinal crypt base stem cells.bioRxiv : the preprint server for biology · 2026Article
- Biological Insights into Intestinal Adaptation from Preclinical Models of Short Bowel Syndrome.Cells · 2026Review
- Synthetically engineered probiotic suppresses colorectal cancer via inhibition of Wnt/β-catenin signaling.Cell reports. Medicine · 2026Article
- Golgi organization regulates stem cell function in the small intestine.Nature communications · 2026Article
- Dynamic Reprogramming of PDGFRA-Expressing Stromal Cells Facilitates WNT-Driven Transformation by Promoting a Fetal-Like State in the Intestinal Epithelium.Cancer research · 2026Article
- Paneth cell SIRT1 deficiency increases intestinal stress resistance by modulating the gut microbiota.EMBO reports · 2026Article
- Paneth cells as orchestrators of epithelial barrier defense and emerging therapeutic targets in inflammatory bowel disease.Seminars in immunopathology · 2026Review
- Prenatal supplementation with the gut-derived tryptophan metabolite indole-3-propionic acid alleviates colitis susceptibility in maternal immune-activated offspring mice.Journal of advanced research · 2026Article
- Intestinal epithelial cells in health and disease.Tissue barriers · 2026Review
- Molecular and Chromatin Accessibility Programs Underlying Epithelial Injury and Impaired Regeneration in Neonatal Necrotizing Enterocolitis.Cellular and molecular gastroenterology and hepatology · 2026Article
- A human intestinal epithelial-mesenchyme-immune triple culture system for disease modelling.Frontiers in cell and developmental biology · 2026Article
- Review
- Hypoxia Affects Stem Cell Fate in Patient-Derived Ileum Enteroids in a HIF-1α-Dependent Manner.Cells · 2025Article
- Epithelial WNT secretion drives niche escape of developing gastric cancer.Molecular cancer · 2025Article
- Arsenic exposure affects Pdgfrα stromal cells in the ileum of the small intestine.Toxicology and applied pharmacology · 2025Article
- Telocytes deliver essential Wnts directly to murine intestinal stem cells via synapse-like contacts.Developmental cell · 2025Article
- Defining the mucosal ecosystem: epithelial-mesenchymal interdependence in gastrointestinal health and disease.Nature reviews. Gastroenterology & hepatology · 2025Review
331 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND &
aimsWnt signaling regulates multiple aspects of intestinal physiology, including stem cell maintenance. Paneth cells support stem cells by secreting Wnt, but little is known about the exact sources and primary functions of individual Wnt family members.
methodsWe analyzed intestinal tissues and cultured epithelial cells from adult mice with conditional deletion of Wnt3 (Vil-CreERT2;Wnt3fl/fl mice). We also analyzed intestinal tissues and cells from Atoh1 mutant mice, which lack secretory cells.
resultsUnexpectedly, Wnt3 was dispensable for maintenance of intestinal stem cells in mice, indicating a redundancy of Wnt signals. By contrast, cultured crypt organoids required Paneth cell-derived Wnt3. Addition of exogenous Wnt, or coculture with mesenchymal cells, restored growth of Vil-CreERT2;Wnt3fl/fl crypt organoids. Intestinal organoids from Atoh1 mutant mice did not grow or form Paneth cells; addition of Wnt3 allowed growth in the absence of Paneth cells. Wnt signaling had a synergistic effect with the Lgr4/5 ligand R-spondin to induce formation of Paneth cells. Mosaic expression of Wnt3 in organoids using a retroviral vector promoted differentiation of Paneth cells in a cell-autonomous manner.
conclusionsWnt is part of a signaling loop that affects homeostasis of intestinal stem and Paneth cells in mice. Wnt3 signaling is required for growth and development of organoid cultures, whereas nonepithelial Wnt signals could provide a secondary physiological source of Wnt.
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