Figure 1. A diagrammatic representation of the colonic crypt compartment and the Notch signaling pathway.

Within the epithelium of the normal colonic mucosa, stem cells are located at the base of the crypts. Following asymmetric division, the daughter cells undergo differentiation and migrate upwards to give rise to transient amplifying cells and terminally differentiated cells. Colonic stem cells generate three types of differentiated cells; the absorptive columnar cells, the hormone-producing enteroendocrine cells, and the mucus-secreting goblet cells. Pericryptal myofibroblasts surround the crypt base, which is thought to comprise a stem cell ‘niche’. These cells regulate epithelial stem cell function by paracrine secretion of growth factors and cytokines. Notch activation is observed within the proliferative zone located within the lower region of the crypt. Meanwhile, KLF4 is expressed in the differentiated epithelial cells at the top half of the crypt. Since Hes 1, the direct transcriptional target of Notch, is a transcriptional repressor of KLF4, it is generally assumed that the KLF4 expression is restricted to the differentiated cryptal cells.