The intestine serves mainly as a place for digestion and absorption and functions as an immune
and endocrine organ. Intestinal stem cells (ISCs) play critical roles in the maintenance of intestinal homeostasis
and regeneration, and a complex of signaling pathways is involved in these processes. The
Notch signaling pathway is induced via distinct cell-to-cell connections, which are activated through the
binding of the Notch ligand on the surface of niche cells to the Notch receptor on ISCs. Numerous studies
have shown the central importance of Notch signaling in the proliferation and differentiation of ISCs.
Here, we summarize the latest research progress on the crucial functions of Notch signaling in maintaining
homeostasis and determining the cell fate of ISCs. Furthermore, the challenges of Notch signaling in
colon cancer therapy strategies are also discussed. Several important questions regarding Notch regulation
of ISCs are proposed.
Keywords: Notch signaling, cell fate decision, Intestinal stem cells, Paneth cells, Hes1, Atoh1
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