ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2012
Distinct levels of Sox9 expression mark colon epithelial stem cells that form colonoids in culture.
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 50 papers.
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Who cites it
50 citing papers in PubMed.
- 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
- Wnt and Treg-Associated Signaling Coordinate Mucosal Regeneration and MALT Formation in a Mouse Model of Chronic Colitis.International journal of molecular sciences · 2026Article
- Impaired intestinal cell proliferation parallels increased senescence after burn injury in aged mice.American journal of physiology. Gastrointestinal and liver physiology · 2026Article
- c-KitCell death and differentiation · 2025Article
- Pancreastatin Inhibition Alters the Colonic Epithelial Cells Profile in a Sex-Dependent Manner.International journal of molecular sciences · 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
- Culture media and format alter cellular composition and barrier integrity of porcine colonoid-derived monolayers.Tissue barriers · 2024Article
- Peripheral Neuron-Organoid Interaction Induces Colonic Epithelial Differentiation via Non-Synaptic Substance P Secretion.International journal of stem cells · 2023Article
- A LGR5 reporter pig model closely resembles human intestine for improved study of stem cells in disease.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
- Establishment of a Novel Colitis-Associated Cancer Mouse Model Showing Flat Invasive Neoplasia.Digestive diseases and sciences · 2023Article
- Article
- Ectopically Localized Epithelial Cell Clumps in Ulcers Are Derived from Reserved Crypt Stem Cells in a Mouse Model of Ulcerative Colitis.Digestive diseases and sciences · 2022Article
- Article
- SHP2 regulates the development of intestinal epithelium by modifying OSTERIXFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- In vitro generation of self-renewing human intestinal epithelia over planar and shaped collagen hydrogels.Nature protocols · 2021Article
- IRF2 maintains the stemness of colonic stem cells by limiting physiological stress from interferon.Scientific reports · 2020Article
- Organoid modelling identifies that DACH1 functions as a tumour promoter in colorectal cancer by modulating BMP signalling.EBioMedicine · 2020Article
- Derivation of adult canine intestinal organoids for translational research in gastroenterology.BMC biology · 2019Article
- Sox4 Promotes Atoh1-Independent Intestinal Secretory Differentiation Toward Tuft and Enteroendocrine Fates.Gastroenterology · 2018Article
- Thrombin modifies growth, proliferation and apoptosis of human colon organoids: a protease-activated receptor 1- and protease-activated receptor 4-dependent mechanism.British journal of pharmacology · 2018Article
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5 authors.
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Abstract
Sox9 is an high-mobility group box transcription factor that is expressed in the stem cell zone of the small intestine and colon. We have previously used a Sox9EGFP mouse model to demonstrate that discrete levels of Sox9 expression mark small intestine epithelial stem cells that form crypt/villus-like structures in a three-dimensional culture system (Formeister EJ, Sionas AL, Lorance DK, Barkley CL, Lee GH, Magness ST. Am J Physiol Gastrointest Liver Physiol 296: G1108-G1118, 2009; Gracz AD, Ramalingam S, Magness ST. Am J Physiol Gastrointest Liver Physiol 298: G590-G600, 2010). In the present study, we hypothesized that discrete levels of Sox9 expression would also mark colonic epithelial stem cells (CESCs). Using the Sox9EGFP mouse model, we show that lower levels of Sox9 mark cells in the transit-amplifying progenitor cell zone, while higher levels of Sox9 mark cells in the colonic crypt base. Furthermore, we demonstrate that variable SOX9 levels persist in cells of colonic adenomas from mice and humans. Cells expressing lower Sox9 levels demonstrate gene expression profiles consistent with more differentiated populations, and cells expressing higher Sox9 levels are consistent with less differentiated populations. When placed in culture, cells expressing the highest levels of Sox9 formed "colonoids," which are defined as bodies of cultured colonic epithelial cells that possess multiple cryptlike structures and a pseudolumen. Cells expressing the highest levels of Sox9 also demonstrate multipotency and self-renewal in vitro, indicating functional stemness. These data suggest a dose-dependent role for Sox9 in normal CESCs and cells comprising colon tumors. Furthermore, distinct Sox9 levels represent a new biomarker to study CESC and progenitor biology in physiological and disease states.
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