We found that in the ubiquitous, but not in the endothelial-specific, Dll4 knockouts, the reduction of Lgr5 and Bmi1 positive tumor stem cell density was accompanied with increased tumor epithelium differentiation with a moderate deviation towards the secretory lineages, probably due to the observed Atoh1 and Klf4 overexpression by Hes1 downregulation as it occurs when Notch signalling is inhibited [8, 63]. The gene discussed is HES1; the disease is neoplasm.