ArticleGut2022
Chief cell plasticity is the origin of metaplasia following acute injury in the stomach mucosa.
Article in Gut, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- Global research trends in signaling pathways of spasmolytic polypeptide-expressing metaplasia pathogenesis: a bibliometric analysis.Frontiers in oncology · 2025Pooled it
- Review
- EradicatingBioactive materials · 2026Article
- The origins and progression of pyloric metaplasia following gastric mucosal injury.Physiological reviews · 2026Review
- Autophagy: Mechanisms and therapeutic perspectives in intestinal metaplasia (Review).Molecular medicine reports · 2026Review
- Gastric Cancer: Pathobiology and Therapeutics.MedComm · 2026Review
- Quantifying the Localization of Histological Staining Markers within the GI Epithelial Unit Axis: A Gastrointestinal Spatial Pathology Plugin for ImageJ.bioRxiv : the preprint server for biology · 2026Article
- Single-nucleus multiome sequencing identifies candidate regulators of mouse gastric epithelial homeostasis.bioRxiv : the preprint server for biology · 2026Article
- Regulation of STK38 by autophagy governs YAP1 activity during paligenosis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Roles of interleukins in spasmolytic polypeptide‑expressing metaplasia (Review).International journal of oncology · 2026Review
- Paligenosis: dual potential of mature cell plasticity in regeneration and tumorigenesis.MedScience · 2026Review
- Lipidomics and single-cell transcriptomics uncover aberrant lipid metabolism in metaplasia lesions during gastric carcinogenesis.Journal of gastroenterology · 2026Article
- Article
- Predictive role of a novel nutrition and inflammation-based model in the short-term clinical outcomes and health-related quality of life of patients undergoing radical gastrectomy: a retrospective cohort study.Discover oncology · 2025Article
- Safety and Efficacy of MEK Inhibitor Treatment for Gastric Precancerous Lesions.Gastroenterology · 2025Article
- Development of Mouse Models for Ménétrier's Disease.Journal of visualized experiments : JoVE · 2025Article
- Helicobacter pylori, microbiota and gastric cancer - principles of microorganism-driven carcinogenesis.Nature reviews. Gastroenterology & hepatology · 2025Review
- H. Pylori-Facilitated TERT/Wnt/β-Catenin Triggers Spasmolytic Polypeptide-Expressing Metaplasia and Oxyntic Atrophy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Cellular lineage origins of spasmolytic polypeptide-expressing metaplasia (SPEM): persistent and intensifying debates.Frontiers in oncology · 2025Review
- Luteolin improves precancerous conditions of the gastric mucosa by binding STAT3 and inhibiting LCN2 expression.International journal of biological sciences · 2025Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
objectiveMetaplasia arises from differentiated cell types in response to injury and is considered a precursor in many cancers. Heterogeneous cell lineages are present in the reparative metaplastic mucosa with response to injury, including foveolar cells, proliferating cells and spasmolytic polypeptide-expressing metaplasia (SPEM) cells, a key metaplastic cell population. Zymogen-secreting chief cells are long-lived cells in the stomach mucosa and have been considered the origin of SPEM cells; however, a conflicting paradigm has proposed isthmal progenitor cells as an origin for SPEM.
designGastric intrinsic factor (GIF) is a stomach tissue-specific gene and exhibits protein expression unique to mature mouse chief cells. We generated a novel chief cell-specific driver mouse allele, GIF-rtTA. GIF-GFP reporter mice were used to validate specificity of GIF-rtTA driver in chief cells. GIF-Cre-RnTnG mice were used to perform lineage tracing during homoeostasis and acute metaplasia development. L635 treatment was used to induce acute mucosal injury and coimmunofluorescence staining was performed for various gastric lineage markers.
resultsWe demonstrated that mature chief cells, rather than isthmal progenitor cells, serve as the predominant origin of SPEM cells during the metaplastic process after acute mucosal injury. Furthermore, we observed long-term label-retaining chief cells at 1 year after the GFP labelling in chief cells. However, only a very small subset of the long-term label-retaining chief cells displayed the reprogramming ability in homoeostasis. In contrast, we identified chief cell-originating SPEM cells as contributing to lineages within foveolar cell hyperplasia in response to the acute mucosal injury.
conclusionOur study provides pivotal evidence for cell plasticity and lineage contributions from differentiated gastric chief cells during acute metaplasia development.
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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.