ArticleCell death & disease2015
TSC2/mTORC1 signaling controls Paneth and goblet cell differentiation in the intestinal epithelium.
Article in Cell death & disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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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
37 citing papers in PubMed, 69 citations in OpenAlex.
- AP-1B Controls Several Levels of Cell Proliferation and Differentiation in Mouse Enteroids.Biology of the cell · 2026Article
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- miR-181a-5p mediates the effects of BMP4 on intestinal cell proliferation and differentiation.Cell death & disease · 2025Article
- miR-27a-3p regulates intestinal cell proliferation and differentiation through Wnt/β-catenin signalling.Cell proliferation · 2025Article
- Cbl and Cbl-b ubiquitin ligases are essential for intestinal epithelial stem cell maintenance.iScience · 2024Article
- Analyzing efficiency of a lentiviral shRNA knockdown system in human enteroids using western blot and flow cytometry.STAR protocols · 2024Article
- Building better barriers: how nutrition and undernutrition impact pediatric intestinal health.Frontiers in immunology · 2023Review
- Optimized human intestinal organoid model reveals interleukin-22-dependency of paneth cell formation.Cell stem cell · 2022Article
- Glycans that regulate Notch signaling in the intestine.Biochemical Society transactions · 2022Review
- Emc3 maintains intestinal homeostasis by preserving secretory lineages.Mucosal immunology · 2021Article
- Acceleration of Small Intestine Development and Remodeling of the Microbiome Following Hyaluronan 35 kDa Treatment in Neonatal Mice.Nutrients · 2021Article
- Monocarboxylate Transporter 4 Triggered Cell Pyroptosis to Aggravate Intestinal Inflammation in Inflammatory Bowel Disease.Frontiers in immunology · 2021Article
- Identification, Characterization, and Transcriptional Reprogramming of Epithelial Stem Cells and Intestinal Enteroids in Simian Immunodeficiency Virus Infected Rhesus Macaques.Frontiers in immunology · 2021Article
- Cell fate specification and differentiation in the adult mammalian intestine.Nature reviews. Molecular cell biology · 2021Review
- Disturbances of the Gut Microbiota, Sleep Architecture, and mTOR Signaling Pathway in Patients with Severe Obstructive Sleep Apnea-Associated Hypertension.International journal of hypertension · 2021Article
- Spectrum of Somatic Cancer Gene Variations Among Adults With Appendiceal Cancer by Age at Disease Onset.JAMA network open · 2020Article
- Plasticity of Paneth cells and their ability to regulate intestinal stem cells.Stem cell research & therapy · 2020Review
- Public Database-Driven Insights Into Aging Stress-Associated Defective Gut Barrier With Low SARS-CoV-2 Receptors.Frontiers in medicine · 2020Article
- SIRT2 Contributes to the Regulation of Intestinal Cell Proliferation and Differentiation.Cellular and molecular gastroenterology and hepatology · 2020Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The intestinal mucosa undergoes a continual process of proliferation, differentiation and apoptosis, which is regulated by multiple signaling pathways. Notch signaling is critical for the control of intestinal stem cell maintenance and differentiation. However, the precise mechanisms involved in the regulation of differentiation are not fully understood. Previously, we have shown that tuberous sclerosis 2 (TSC2) positively regulates the expression of the goblet cell differentiation marker, MUC2, in intestinal cells. Using transgenic mice constitutively expressing a dominant negative TSC2 allele, we observed that TSC2 inactivation increased mTORC1 and Notch activities, and altered differentiation throughout the intestinal epithelium, with a marked decrease in the goblet and Paneth cell lineages. Conversely, treatment of mice with either Notch inhibitor dibenzazepine (DBZ) or mTORC1 inhibitor rapamycin significantly attenuated the reduction of goblet and Paneth cells. Accordingly, knockdown of TSC2 activated, whereas knockdown of mTOR or treatment with rapamycin decreased, the activity of Notch signaling in the intestinal cell line LS174T. Importantly, our findings demonstrate that TSC2/mTORC1 signaling contributes to the maintenance of intestinal epithelium homeostasis by regulating Notch activity.
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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.