Notch signalling maintainsintestinal stem cells In addition to repressing thesecretory cell phenotype, notch signalling has been implicated in maintainingthe proliferative state of intestinal progenitors and stem cells.Co-localisation of Hes1, with the intestinal stem cell marker Musashi-1 (Msi1)in cells at the bottom of the crypt, indicated the presence of notch activityin CBC’s. A similar observation was made at the +4 stem cells in the smallintestine. Lineage tracing studies using a tamoxifen induced Notch1 Cre-mousemodel (NIP1::CreERT2) revealed that, after eight months, labelledcells occupied the entire crypt (and villus) and expressed markers of all thedifferentiated cell types in the adult intestine (Pellegrinet et al, 2012). This showed that cells expressing Notch1activity were capable of self-renewal and differentiation, therefore,expressing stem-cell properties. A lower number of Notch1 labelled cells werefound in the colon as compared to the small intestine. This phenomenon issimilar to the aforementioned observation in Lgr5 lineage tracing experiments,where slower cycling rates were attributed to colonic CBC’s (Barker etal,2007).
The discovery of Lgr5 as a unique marker of CBC’s paved way for the identificationof Notch activity in intestinal stem cells as well. Dll1 and Dll4 double knockoutand RBP-J inactivated mice, along with increased goblet cell numbers, lost theexpression of stem cell markers including Lgr5, Olfm4 and Ascl2. Furthermore,proliferating Ki67-positive cells in the crypts were ablated (Pellegrinet etal, 2012).