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Mouse fetal intestinal organoids: new model to study epithelial maturation from suckling to weaning

During the suckling‐to‐weaning transition, the intestinal epithelium matures, allowing digestion of solid food. Transplantation experiments with rodent fetal epithelium into subcutaneous tissue of adult animals suggest that this transition is intrinsically programmed and occurs in the absence of die...

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Bibliographic Details
Published in:EMBO reports 2019-02, Vol.20 (2), p.n/a
Main Authors: Navis, Marit, Martins Garcia, Tânia, Renes, Ingrid B, Vermeulen, Jacqueline LM, Meisner, Sander, Wildenberg, Manon E, van den Brink, Gijs R, van Elburg, Ruurd M, Muncan, Vanesa
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Language:English
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Summary:During the suckling‐to‐weaning transition, the intestinal epithelium matures, allowing digestion of solid food. Transplantation experiments with rodent fetal epithelium into subcutaneous tissue of adult animals suggest that this transition is intrinsically programmed and occurs in the absence of dietary or hormonal signals. Here, we show that organoids derived from mouse primary fetal intestinal epithelial cells express markers of late fetal and neonatal development. In a stable culture medium, these fetal epithelium‐derived organoids lose all markers of neonatal epithelium and start expressing hallmarks of adult epithelium in a time frame that mirrors epithelial maturation in vivo. In vitro postnatal development of the fetal‐derived organoids accelerates by dexamethasone, a drug used to accelerate intestinal maturation in vivo. Together, our data show that organoids derived from fetal epithelium undergo suckling‐to‐weaning transition, that the speed of maturation can be modulated, and that fetal organoids can be used to model the molecular mechanisms of postnatal epithelial maturation. Synopsis Organoids derived from mouse primary fetal intestinal epithelial cells undergo suckling‐to‐weaning transition independent of stromal cells and can be used to model the molecular mechanisms of postnatal epithelial development. Mouse fetal intestinal organoids undergo the suckling‐to‐weaning transition in vitro. Fetal intestinal organoids express functional adult brush border enzymes over time. Dexamethasone can accelerate intestinal epithelial maturation in vitro. Fetal intestinal organoids can be used to model postnatal epithelial development. Organoids derived from mouse primary fetal intestinal epithelial cells undergo suckling‐to‐weaning transition independent of stromal cells and can be used to model the molecular mechanisms of postnatal epithelial development.
ISSN:1469-221X
1469-3178
DOI:10.15252/embr.201846221