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Organoids as a Model System for Studying Notch Signaling in Intestinal Epithelial Homeostasis and Intestinal Cancer

      Abstract

      Organoid culture is an approach that allows three-dimensional growth for stem cells to self-organize and develop multicellular structures. Intestinal organoids have been widely used to study cellular or molecular processes in stem cell and cancer research. These cultures possess the ability to maintain cellular complexity as well as recapitulate many properties of the human intestinal epithelium, thereby providing an ideal in vitro model to investigate cellular and molecular signaling pathways. These include, but are not limited to, the mechanisms required for maintaining balanced populations of epithelial cells. Notch signaling is one of the major pathways of regulating stem cell functions in the gut driving proliferation and controlling cell fate determination. Notch also plays an important role in regulating tumor progression and metastasis. Understanding how Notch pathway regulates epithelial regeneration and differentiation by using intestinal organoids is critical for studying both homeostasis and pathogenesis of intestinal stem cells (ISCs) that can lead to discoveries of new targets for drug development to treat intestinal diseases. Additionally, use of patient-derived organoids can provide effective personalized medicine. In this review, we summarize the current literature regarding epithelial Notch pathways regulating intestinal homeostasis and regeneration, highlighting the use of organoid cultures and their potential therapeutic applications.
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