Notch/γ-secretase inhibition turns proliferative cells in intestinal crypts and adenomas into goblet cells

By J. V. Es, M. E. Gijn, O. Riccio, M. V. D. Born, M. Vooijs, H. Begthel, M. Cozijnsen, S. Robine, D. Winton, Freddy Radtke and 1 more. Nature, 2005

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Wnt signaling in cancer. (2012, result): “The impact of Notch in the intestine was consistent with previous work showing that its activation or inhibition increased or decreased the population of proliferating/progenitor cells, respectively, at the expense of the differentiated population (Fre et al. 2005; van Es et al. 2005).”
Notch pathway inhibition depletes stem-like cells and blocks engraftment in embryonal brain tumors. (2006, background): “been linked to cellular differentiation in both normal development and in neoplasms (42, 43) and we therefore examined whether Notch inhibition caused cellular differentiation.”
The intestinal crypt, a prototype stem cell compartment. (2013, background): “Indeed, Hes1 is expressed in most proliferative crypt cells, whereas Math1 is only seen in secretory cells; inhibition of Notch signaling rapidly leads to loss of Hes1 expression and to the consequent induction of Math1 expression in all crypt cells (van Es et al., 2005b).”
Epithelial stem cells: turning over new leaves. (2007, positive): “Notably, hair keratin genes are transcriptionally regulated by Lef1/ β-catenin (Merrill et al., 2001) and expression of genes specific to Paneth cells, such as cryptidin/defensins, is lost upon deletion of Tcf4 or Wnt receptor Frizzled 5 (van Es et al., 2005a).”