ArticleGastroenterology2015
SOX9 maintains reserve stem cells and preserves radioresistance in mouse small intestine.
Article in Gastroenterology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers.
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Who cites it
114 citing papers in PubMed, 182 citations in OpenAlex.
- Building and regenerating intestines by manipulating intestinal stem cells.Nature reviews. Gastroenterology & hepatology · 2026Review
- Identification of stem cell marker-positive subpopulations in the vocal fold of the larynx through transcriptomic analyses.Nature communications · 2026Article
- Intrinsic mechanisms and microenvironmental cues fine-tune plasticity of esophageal progenitors.Nature communications · 2026Article
- G9a-mediated H3K9me2 orchestrates intestinal epithelial regeneration through epigenetic silencing of cell cycle-related genes.Nature communications · 2026Article
- Wnt and Treg-Associated Signaling Coordinate Mucosal Regeneration and MALT Formation in a Mouse Model of Chronic Colitis.International journal of molecular sciences · 2026Article
- Optimising the induction of inflammation within preterm infant-derived intestinal epithelial organoids.Npj gut and liver · 2026Article
- Roles of intestinal stem cells in inflammatory bowel disease pathogenesis.World journal of stem cells · 2025Review
- SOX9: an important factor in regulating breast cancer.European journal of medical research · 2025Review
- Single-cell transcriptomics reveals BMP4-BMPR2 signaling promotes radiation resistance in hematopoietic stem cells following injury.Nature communications · 2025Article
- The Impact of Imidacloprid in Dietary Residues on Intestinal Damage and the Increased Risk of EnterotoxigenicFoods (Basel, Switzerland) · 2025Article
- Tet1 safeguards lineage allocation in intestinal stem cells.bioRxiv : the preprint server for biology · 2025Article
- Diprovocim protects against the radiation-induced damage via the TLR2 signaling pathway.Molecular medicine (Cambridge, Mass.) · 2025Article
- Intestinal stem cell niche: An upcoming area of immense importance in gastrointestinal disorders.Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology · 2025Review
- Characterizing Duodenal Immune Microenvironment in Functional Dyspepsia: An AutoML-Driven Diagnostic Framework.Journal of inflammation research · 2025Article
- Article
- Obese Adipose Tissue Extracellular Vesicles Activate Mitochondrial Fatty Acid β-oxidation to Drive Colonic Stemness.Cellular and molecular gastroenterology and hepatology · 2025Article
- Lgr5 + intestinal stem cells are required for organoid survival after genotoxic injury.Development (Cambridge, England) · 2024Article
- 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
- Aloe emodin promotes mucosal healing by modifying the differentiation fate of enteroendocrine cellsActa pharmaceutica Sinica. B · 2024Article
- Navigating the Landscape of Intestinal Regeneration: A Spotlight on Quiescence Regulation and Fetal Reprogramming.International journal of stem cells · 2024Review
54 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsReserve intestinal stem cells (rISCs) are quiescent/slowly cycling under homeostatic conditions, allowing for their identification with label-retention assays. rISCs mediate epithelial regeneration after tissue damage by converting to actively proliferating stem cells (aISCs) that self renew and demonstrate multipotency, which are defining properties of stem cells. Little is known about the genetic mechanisms that regulate the production and maintenance of rISCs. High expression levels of the transcription factor Sox9 (Sox9(high)) are associated with rISCs. This study investigates the role of SOX9 in regulating the rISC state.
methodsWe used fluorescence-activated cell sorting to isolate cells defined as aISCs (Lgr5(high)) and rISCs (Sox9(high)) from Lgr5(EGFP) and Sox9(EGFP) reporter mice. Expression of additional markers associated with active and reserve ISCs were assessed in Lgr5(high) and Sox9(high) populations by single-cell gene expression analyses. We used label-retention assays to identify whether Sox9(high) cells were label-retatining cells (LRCs). Lineage-tracing experiments were performed in Sox9-CreERT2 mice to measure the stem cell capacities and radioresistance of Sox9-expressing cells. Conditional SOX9 knockout mice and inducible-conditional SOX9 knockout mice were used to determine whether SOX9 was required to maintain LRCs and rISC function.
resultsLgr5(high) and a subset of crypt-based Sox9(high) cells co-express markers of aISC and rISC (Lgr5, Bmi1, Lrig1, and Hopx). LRCs express high levels of Sox9 and are lost in SOX9-knockout mice. SOX9 is required for epithelial regeneration after high-dose irradiation. Crypts from SOX9-knockout mice have increased sensitivity to radiation, compared with control mice, which could not be attributed to impaired cell-cycle arrest or DNA repair.
conclusionsSOX9 limits proliferation in LRCs and imparts radiation resistance to rISCs in mice.
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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.