ArticleCell stem cell2020
A Metformin-Responsive Metabolic Pathway Controls Distinct Steps in Gastric Progenitor Fate Decisions and Maturation.
Article in Cell stem cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
What it found
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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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
40 citing papers in PubMed, 64 citations in OpenAlex.
- Therapeutic effect of metformin on reversing gastric intestinal metaplasia.Chinese medical journal · 2026Trial
- The origins and progression of pyloric metaplasia following gastric mucosal injury.Physiological reviews · 2026Review
- Stomach at the crossroads: nuclear receptor signaling at the interface between what we are and what we eat.Physiological reviews · 2026Review
- Paligenosis: dual potential of mature cell plasticity in regeneration and tumorigenesis.MedScience · 2026Review
- The Diverse Roles of Mitochondria in Regulating Cancer Metastasis.Current issues in molecular biology · 2025Review
- The critical role of BMP signaling in gastric epithelial cell differentiation revealed by organoids.Cell regeneration (London, England) · 2025Article
- Standard: Human gastric organoids.Cell regeneration (London, England) · 2025Article
- H. Pylori-Facilitated TERT/Wnt/β-Catenin Triggers Spasmolytic Polypeptide-Expressing Metaplasia and Oxyntic Atrophy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Procaine induces cell cycle arrest, apoptosis and autophagy through the inhibition of the PI3K/AKT and ERK pathways in human tongue squamous cell carcinoma.Oncology letters · 2024Article
- Amphiregulin Switches Progenitor Cell Fate for Lineage Commitment During Gastric Mucosal Regeneration.Gastroenterology · 2024Article
- Aging-associated decrease of PGC-1α promotes pain chronification.Aging cell · 2024Article
- Metabolic regulator ERRγ governs gastric stem cell differentiation into acid-secreting parietal cells.Cell stem cell · 2024Article
- Success rate of current human-derived gastric cancer organoids establishment and influencing factors: A systematic review and meta-analysis.World journal of gastrointestinal oncology · 2024Article
- Gastric intestinal metaplasia: progress and remaining challenges.Journal of gastroenterology · 2024Review
- Energy metabolism: a new target for gastric cancer treatment.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Review
- Revealing the role of metformin in gastric intestinal metaplasia treatment.Frontiers in pharmacology · 2024Article
- Molecular mechanisms of cellular metabolic homeostasis in stem cells.International journal of oral science · 2023Review
- Single-cell transcriptomics uncovers EGFR signaling-mediated gastric progenitor cell differentiation in stomach homeostasis.Nature communications · 2023Article
- Article
- Comprehensive Comparisons between Grafted Kynam Agarwood and Normal Agarwood on Traits, Composition, and In Vitro Activation of AMPK.Molecules (Basel, Switzerland) · 2023Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Cellular metabolism plays important functions in dictating stem cell behaviors, although its role in stomach epithelial homeostasis has not been evaluated in depth. Here, we show that the energy sensor AMP kinase (AMPK) governs gastric epithelial progenitor differentiation. Administering the AMPK activator metformin decreases epithelial progenitor proliferation and increases acid-secreting parietal cells (PCs) in mice and organoids. AMPK activation targets Krüppel-like factor 4 (KLF4), known to govern progenitor proliferation and PC fate choice, and PGC1α, which we show controls PC maturation after their specification. PC-specific deletion of AMPKα or PGC1α causes defective PC maturation, which could not be rescued by metformin. However, metformin treatment still increases KLF4 levels and suppresses progenitor proliferation. Thus, AMPK activates KLF4 in progenitors to reduce self-renewal and promote PC fate, whereas AMPK-PGC1α activation within the PC lineage promotes maturation, providing a potential suggestion for why metformin increases acid secretion and reduces gastric cancer risk in humans.
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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.