ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2018
Mature enteroendocrine cells contribute to basal and pathological stem cell dynamics in the small intestine.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 39 citations in OpenAlex.
- Global Trends in Research of Intestinal Cells and Type 2 Diabetes Mellitus: A Bibliometric and Visualized Analysis from 2004 to 2023.Endocrine, metabolic & immune disorders drug targets · 2026Review
- Intestinal epithelial cells in health and disease.Tissue barriers · 2026Review
- Dietary Stearic Acid Accelerates Intestinal Tumorigenesis via Fatty Acid-binding Protein 5 Without Promoting Obesity.Cellular and molecular gastroenterology and hepatology · 2026Article
- Roles of intestinal stem cells in inflammatory bowel disease pathogenesis.World journal of stem cells · 2025Review
- The IL-18 receptor is expressed on murine small-intestinal enterochromaffin cells and executes a recovery program upon injury.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
- A Lgr5-independent developmental lineage is involved in mouse intestinal regeneration.Development (Cambridge, England) · 2025Article
- Enteroendocrine cells regulate intestinal homeostasis and epithelial function.Molecular and cellular endocrinology · 2024Review
- Navigating the Landscape of Intestinal Regeneration: A Spotlight on Quiescence Regulation and Fetal Reprogramming.International journal of stem cells · 2024Review
- Tissue- and cell-specific properties of enterochromaffin cells affect the fate of tumorigenesis toward nonendocrine adenocarcinoma of the small intestine.American journal of physiology. Gastrointestinal and liver physiology · 2023Article
- SIRT1 Controls Enteroendocrine Progenitor Cell Proliferation in High-Fat Diet-Fed Mice.Cellular and molecular gastroenterology and hepatology · 2023Article
- Autophagic state prospectively identifies facultative stem cells in the intestinal epithelium.EMBO reports · 2022Article
- Limitations to Understanding Intestinal Stem Cell Activity via Cre-Lox-Based Lineage Tracing.Cellular and molecular gastroenterology and hepatology · 2022Article
- The distribution and chemical coding of enteroendocrine cells in Trypanosoma cruzi-infected individuals with chagasic megacolon.Histochemistry and cell biology · 2021Article
- Subversion of Niche-Signalling Pathways in Colorectal Cancer: What Makes and Breaks the Intestinal Stem Cell.Cancers · 2021Review
- Role of an active reserve stem cell subset of enteroendocrine cells in intestinal stem cell dynamics and the genesis of small intestinal neuroendocrine tumors.American journal of physiology. Gastrointestinal and liver physiology · 2020Review
- Elevating EGFR-MAPK program by a nonconventional Cdc42 enhances intestinal epithelial survival and regeneration.JCI insight · 2020Article
- Plasticity of Paneth cells and their ability to regulate intestinal stem cells.Stem cell research & therapy · 2020Review
- Rapid Crypt Cell Remodeling Regenerates the Intestinal Stem Cell Niche after Notch Inhibition.Stem cell reports · 2020Article
- celsr1a is essential for tissue homeostasis and onset of aging phenotypes in the zebrafish.eLife · 2020Article
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 1 country.
Funding
Abstract
Lgr5-expressing intestinal stem cells (ISCs) maintain continuous and rapid generation of the intestinal epithelium. Here, we present evidence that dedifferentiation of committed enteroendocrine cells (EECs) contributes to maintenance of the epithelium under both basal conditions and in response to injury. Lineage-tracing studies identified a subset of EECs that reside at +4 position for more than 2 wk, most of which were BrdU-label-retaining cells. Under basal conditions, cells derived from these EECs grow from the bottom of the crypt to generate intestinal epithelium according to neutral drift kinetics that is consistent with dedifferentiation of mature EECs to ISCs. The lineage tracing of EECs demonstrated reserve stem cell properties in response to radiation-induced injury with the generation of reparative EEC-derived epithelial patches. Finally, the enterochromaffin (EC) cell was the predominant EEC type participating in these stem cell dynamics. These results provide novel insights into the +4 reserve ISC hypothesis, stem cell dynamics of the intestinal epithelium, and in the development of EC-derived small intestinal tumors. NEW & NOTEWORTHY The current manuscript demonstrating that a subset of mature enteroendocrine cells (EECs), predominantly enterochromaffin cells, dedifferentiates to fully functional intestinal stem cells (ISCs) is novel, timely, and important. These cells dedifferentiate to ISCs not only in response to injury but also under basal homeostatic conditions. These novel findings provide a mechanism in which a specified cell can dedifferentiate and contribute to normal tissue plasticity as well as the development of EEC-derived intestinal tumors under pathologic conditions.
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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.