ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2012
Activation of two distinct Sox9-EGFP-expressing intestinal stem cell populations during crypt regeneration after irradiation.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers.
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Who cites it
103 citing papers in PubMed, 141 citations in OpenAlex.
- A Rare T-Cell Factor 4 Lineage-negative Epithelial Stem Cell Supports Wound Repair and APC-deletion-induced Colon Tumorigenesis.bioRxiv : the preprint server for biology · 2026Article
- Unveiling the neutrophil-Notch2-ISC axis: asiatic acid's therapeutic strategy in infectious colitis.Frontiers in immunology · 2025Article
- Anorectal Remodeling in the Transitional Zone with Increased Expression of LGR5, SOX9, SOX2, and Keratin 13 and 5 in a Dextran Sodium Sulfate-Induced Mouse Model of Ulcerative Colitis.International journal of molecular sciences · 2024Article
- 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
- METI: deep profiling of tumor ecosystems by integrating cell morphology and spatial transcriptomics.Nature communications · 2024Article
- Chronic arsenic exposure affects stromal cells and signaling in the small intestine in a sex-specific manner.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- Organ Boundary Circuits Regulate Sox9+ Alveolar Tuft Cells During Post-Pneumonectomy Lung Regeneration.bioRxiv : the preprint server for biology · 2024Article
- Building better barriers: how nutrition and undernutrition impact pediatric intestinal health.Frontiers in immunology · 2023Review
- Prenatal stress induces changes in PAR2- and M3-dependent regulation of colon primitive cells.American journal of physiology. Gastrointestinal and liver physiology · 2022Article
- Stem cell therapy as a promising strategy in necrotizing enterocolitis.Molecular medicine (Cambridge, Mass.) · 2022Review
- Intestinal Epithelial Regeneration in Response to Ionizing Irradiation.Journal of visualized experiments : JoVE · 2022Article
- Transplanted hair follicle mesenchymal stem cells alleviated small intestinal ischemia-reperfusion injuryFrontiers in cell and developmental biology · 2022Article
- HOPXAmerican journal of physiology. Gastrointestinal and liver physiology · 2021Article
- Wnt and Src signals converge on YAP-TEAD to drive intestinal regeneration.The EMBO journal · 2021Article
- Honokiol Affects Stem Cell Viability by Suppressing Oncogenic YAP1 Function to Inhibit Colon Tumorigenesis.Cells · 2021Article
- CREPT is required for murine stem cell maintenance during intestinal regeneration.Nature communications · 2021Article
- SHP2 regulates the development of intestinal epithelium by modifying OSTERIXFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- PCSK9 is not secreted from mature differentiated intestinal cells.Journal of lipid research · 2021Article
- Use of organoids to study regenerative responses to intestinal damage.American journal of physiology. Gastrointestinal and liver physiology · 2019Review
43 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Recent identification of intestinal epithelial stem cell (ISC) markers and development of ISC reporter mice permit visualization and isolation of regenerating ISCs after radiation to define their functional and molecular phenotypes. Previous studies in uninjured intestine of Sox9-EGFP reporter mice demonstrate that ISCs express low levels of Sox9-EGFP (Sox9-EGFP Low), whereas enteroendocrine cells (EEC) express high levels of Sox9-EGFP (Sox9-EGFP High). We hypothesized that Sox9-EGFP Low ISCs would expand after radiation, exhibit enhanced proliferative capacities, and adopt a distinct gene expression profile associated with rapid proliferation. Sox9-EGFP mice were given 14 Gy abdominal radiation and studied between days 3 and 9 postradiation. Radiation-induced changes in number, growth, and transcriptome of the different Sox9-EGFP cell populations were determined by histology, flow cytometry, in vitro culture assays, and microarray. Microarray confirmed that nonirradiated Sox9-EGFP Low cells are enriched for Lgr5 mRNA and mRNAs enriched in Lgr5-ISCs and identified additional putative ISC markers. Sox9-EGFP High cells were enriched for EEC markers, as well as Bmi1 and Hopx, which are putative markers of quiescent ISCs. Irradiation caused complete crypt loss, followed by expansion and hyperproliferation of Sox9-EGFP Low cells. From nonirradiated intestine, only Sox9-EGFP Low cells exhibited ISC characteristics of forming organoids in culture, whereas during regeneration both Sox9-EGFP Low and High cells formed organoids. Microarray demonstrated that regenerating Sox9-EGFP High cells exhibited transcriptomic changes linked to p53-signaling and ISC-like functions including DNA repair and reduced oxidative metabolism. These findings support a model in which Sox9-EGFP Low cells represent active ISCs, Sox9-EGFP High cells contain radiation-activatable cells with ISC characteristics, and both participate in crypt regeneration.
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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.