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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Article Info
Publication History
Accepted:
June 7,
2022
Received in revised form:
May 16,
2022
Received:
March 9,
2022
Publication stage
In Press Journal Pre-ProofFootnotes
Sources of support: This work was supported in part by research funding from NCI CA222064 and NIH HL103827 (to LZ), and by the Department of Pathology Case Western Reserve University faculty startup fund to LZ.
Disclosure of Potential Conflicts of Interest: The authors have declared that no conflict of interest exists.
Identification
Copyright
© 2022 Published by Elsevier Inc. on behalf of the American Society for Investigative Pathology.