Notch regulation of gastrointestinal stem cells

The gastrointestinal (GI) tract epithelium is continuously replenished by actively cycling stem and progenitor cells. These cell compartments are regulated to balance proliferation and stem cell renewal with differentiation into the various mature cell types to maintain tissue homeostasis. In this topical review we focus on the role of the Notch signalling pathway to regulate GI stem cell function in adult small intestine and stomach. We first present the current view of stem and progenitor cell populations in these tissues and then summarize the studies that have established the Notch pathway as a key regulator of gastric and intestinal stem cell function. Notch signalling has been shown to be a niche factor required for maintenance of GI stem cells in both tissues. In addition, Notch has been described to regulate epithelial cell differentiation. Recent studies have revealed key similarities and differences in how Notch regulates stem cell function in the stomach compared to intestine. We summarize the literature regarding Notch regulation of GI stem cell proliferation and differentiation, highlighting tissue‐specific functions to compare and contrast Notch in the stomach and intestine.Notch regulation of intestinal epithelial cell homeostasis. A, during homeostatic conditions, Notch maintains the intestinal stem cell (SC) pool and promotes proliferation of a multi‐potential (MP) progenitor cell that will further differentiate into an absorptive progenitor (AP) or secretory progenitor (SP) cell in the intestine. Therefore, Notch is required to maintain the balance of stem cell proliferation and differentiation. B, during Notch inhibition, stem cell proliferation is reduced and progenitor cells are fated towards the secretory lineage. This results in a net reduction in proliferation and increased secretory cell differentiation. C, in contrast, Notch activation leads to expansion of the stem cell compartment, resulting in increased stem cell proliferation and an overall reduction in epithelial cell differentiation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134111/1/tjp7117.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134111/2/tjp7117_am.pd