Fig. 1.

Sepp1 ^−/− enteroids demonstrate increased stem-cell characteristics. This schematic shows normal growth characteristics upon plating single intestinal crypts. Proliferating cells (red asterisk) include stem cells (CBCs, crypt-based columnar cells) and transient amplifying (TA) cells. Upon differentiation, cells no longer proliferate but complete the crypt structure. When WNT is added to the Matrigel matrix, an increased propensity to form stem spheroids occurs. Once WNT has been expended, enteroids proliferate and component cells differentiate. In the case of Sepp1 knockout, enteroids form more stem spheroids, indicative of increased WNT tone. Sepp1 ^−/− enteroids also demonstrate increased branching, which suggests a higher percentage of stem cells within the population, and higher proliferation even in regions, where cells should be differentiated and quiescent. All these characteristics indicate that loss of SEPP1 contributes to increased tumorigenic properties in epithelial cells