ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2010
Cooperation between HNF-1alpha, Cdx2, and GATA-4 in initiating an enterocytic differentiation program in a normal human intestinal epithelial progenitor cell line.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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38 citing papers in PubMed, 71 citations in OpenAlex.
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- The dopamine transporter antagonist vanoxerine inhibits G9a and suppresses cancer stem cell functions in colon tumors.Nature cancer · 2024Article
- The Combination of Gold and Silver Food Nanoparticles with Gluten Peptides Alters the Autophagic Pathway in Intestinal Crypt-like Cells.International journal of molecular sciences · 2023Article
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- Simian Immunodeficiency Virus Infection Mediated Changes in Jejunum and Peripheral SARS-CoV-2 Receptor ACE2 and Associated Proteins or Genes in Rhesus Macaques.Frontiers in immunology · 2022Article
- Weaning stress and intestinal health of piglets: A review.Frontiers in immunology · 2022Review
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- P63 Deficiency and CDX2 Overexpression Lead to Barrett's-Like Metaplasia in Mouse Esophageal Epithelium.Digestive diseases and sciences · 2021Article
- Src family kinases inhibit differentiation of intestinal epithelial cells through the Hippo effector YAP1.Biology open · 2021Article
- Targeting SUMOylation dependency in human cancer stem cells through a unique SAE2 motif revealed by chemical genomics.Cell chemical biology · 2021Article
- Chromatin Dynamics in Intestinal Epithelial Homeostasis: A Paradigm of Cell Fate Determination versus Cell Plasticity.Stem cell reviews and reports · 2020Review
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- Loss of mismatch repair signaling impairs the WNT-bone morphogenetic protein crosstalk and the colonic homeostasis.Journal of molecular cell biology · 2020Article
- The H2A.Z histone variant integrates Wnt signaling in intestinal epithelial homeostasis.Nature communications · 2019Article
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- CDX2 Stimulates the Proliferation of Porcine Intestinal Epithelial Cells by Activating the mTORC1 and Wnt/β-Catenin Signaling Pathways.International journal of molecular sciences · 2017Article
- Acute myeloid leukaemia disrupts endogenous myelo-erythropoiesis by compromising the adipocyte bone marrow niche.Nature cell biology · 2017Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
In the intestinal epithelium, the Cdx, GATA, and HNF transcription factor families are responsible for the expression of differentiation markers such as sucrase-isomaltase. Although previous studies have shown that Cdx2 can induce differentiation in rat intestinal IEC-6 cells, no data are available concerning the direct implication of transcription factors on differentiation in human normal intestinal epithelial cell types. We investigated the role of Cdx2, GATA-4, and HNF-1alpha using the undifferentiated human intestinal epithelial crypt cell line HIEC. These transcription factors were tested on proliferation and expression of polarization and differentiation markers. Ectopic expression of Cdx2 or HNF-1alpha, alone or in combination, altered cell proliferation abilities through the regulation of cyclin D1 and p27 expression. HNF-1alpha and GATA-4 together induced morphological modifications of the cells toward polarization, resulting in the appearance of functional features such as microvilli. HNF-1alpha was also sufficient to induce the expression of cadherins and dipeptidylpeptidase, whereas in combination with Cdx2 it allowed the expression of the late differentiation marker sucrase-isomaltase. Large-scale analysis of gene expression confirmed the cooperative effect of these factors. Finally, although DcamKL1 and Musashi-1 expression were downregulated in differentiated HIEC, other intestinal stem cell markers, such as Bmi1, were unaffected. These observations show that, in cooperation with Cdx2, HNF-1alpha acts as a key factor on human intestinal cells to trigger the onset of their functional differentiation program whereas GATA-4 appears to promote morphological changes.
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