ArticleGastroenterology2011
Dll1- and dll4-mediated notch signaling are required for homeostasis of intestinal stem cells.
Article in Gastroenterology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 243 papers.
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Who cites it
243 citing papers in PubMed, 413 citations in OpenAlex.
- Nitric Oxide in the Intestinal Stem Cell Niche: A Spatial Model of Nitrosative Stress and Clonal Evolution in Colitis-Associated Colorectal Cancer.Digestive diseases and sciences · 2026Review
- Paneth cell-derived Notch ligands DLL1 and DLL4 are crucial for intestinal crypt base stem cells.bioRxiv : the preprint server for biology · 2026Article
- Endodermal Organoids Along Two Axes: Single-Organ Fidelity, Inter-Organ Reconstruction, and the Unbuilt Gut-Lung Frontier.Stem cell reviews and reports · 2026Review
- Porcine intestinal goblet cells: Guardians of mucosal immunity and barrier function.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2026Review
- Golgi organization regulates stem cell function in the small intestine.Nature communications · 2026Article
- Single-nucleus interrogation of primate small intestinal aging reveals NCoR1 decline as a conserved feature that is reversed by metformin.Nature aging · 2026Article
- Functional genomics analysis of developing zebrafish and human endoderm reveals highly conservedGenome research · 2026Article
- Comparable expression of stem markers and damage-responsive proteins in untreated and chemoradiation-treated rectal cancer.Histology and histopathology · 2026Article
- Paneth cells as orchestrators of epithelial barrier defense and emerging therapeutic targets in inflammatory bowel disease.Seminars in immunopathology · 2026Review
- Hypoxia Affects Stem Cell Fate in Patient-Derived Ileum Enteroids in a HIF-1α-Dependent Manner.Cells · 2025Article
- Developmental regulation of intestinalbioRxiv : the preprint server for biology · 2025Article
- Article
- Identification of intestinal enteroendocrine cell subtypes and their associated hormones in zebrafish.PLoS biology · 2025Article
- Lactoferrin and Osteopontin Cooperatively Promote Intestinal Epithelial Maturation in Neonatal Mice by Activating the Brg1/Notch1/Hes1 Pathway.Nutrients · 2025Article
- Review
- Roles of intestinal stem cells in inflammatory bowel disease pathogenesis.World journal of stem cells · 2025Review
- Evidence of secondary Notch signaling within the rat small intestine.Development (Cambridge, England) · 2025Article
- Article
- Neonatal hypoxia leads to impaired intestinal function and changes in the composition and metabolism of its microbiota.Scientific reports · 2025Article
- H3K36 methylation regulates cell plasticity and regeneration in the intestinal epithelium.Nature cell biology · 2025Article
183 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 5 institutions in 4 countries.
Funding
Abstract
BACKGROUND &
aimsAblation of Notch signaling within the intestinal epithelium results in loss of proliferating crypt progenitors due to their conversion into postmitotic secretory cells. We aimed to confirm that Notch was active in stem cells (SCs), investigate consequences of loss of Notch signaling within the intestinal SC compartment, and identify the physiologic ligands of Notch in mouse intestine. Furthermore, we investigated whether the induction of goblet cell differentiation that results from loss of Notch requires the transcription factor Krüppel-like factor 4 (Klf4).
methodsTransgenic mice that carried a reporter of Notch1 activation were used for lineage tracing experiments. The in vivo functions of the Notch ligands Jagged1 (Jag1), Delta-like1 (Dll1), Delta-like4 (Dll4), and the transcription factor Klf4 were assessed in mice with inducible, gut-specific gene targeting (Vil-Cre-ER(T2)).
resultsNotch1 signaling was found to be activated in intestinal SCs. Although deletion of Jag1 or Dll4 did not perturb the intestinal epithelium, inactivation of Dll1 resulted in a moderate increase in number of goblet cells without noticeable effects of progenitor proliferation. However, simultaneous inactivation of Dll1 and Dll4 resulted in the complete conversion of proliferating progenitors into postmitotic goblet cells, concomitant with loss of SCs (Olfm4(+), Lgr5(+), and Ascl2(+)). Klf4 inactivation did not interfere with goblet cell differentiation in adult wild-type or in Notch pathway-deficient gut.
conclusionsNotch signaling in SCs and progenitors is activated by Dll1 and Dll4 ligands and is required for maintenance of intestinal progenitor and SCs. Klf4 is dispensable for goblet cell differentiation in intestines of adult Notch-deficient mice.
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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.