Novel modelling strategies can integrate the dynamics of processes regulating the intestinal epithelium at multiple scales in homeostasis and following perturbations to provide unprecedented insights into the biology of the epithelium and support the development of safer novel drug candidates.
Fringe proteins regulate Notch pathway differentially in the stem cell zone and progenitor compartment of the mouse intestinal epithelium to promote homeostasis.
Yifan Wang, C Richard Boland ... Natalia L Komarova
A mathematical model of colorectal cancer initiation shows that a change in cells’ kinetic parameters due to aspirin can account for an observed reduction in advanced adenoma age- incidence in patients treated with aspirin.
Guizela Huelsz-Prince, Rutger Nico Ulbe Kok ... Jeroen S van Zon
Tracking of all cells in intestinal organoids crypts to fully reconstruct cell lineages reveals that proliferative behavior is highly symmetric between sisters cells, while simulations show that this observed symmetry minimizes random fluctuations in cell proliferation, thereby ensuring homeostasis.
An enhancer-dependent transcriptional machinery finely tunes the expression of Ctnnb1 in intestinal crypts, thereby balancing homeostasis and tumorigenesis of intestinal epithelia.
miR-31 drives proliferation of intestinal stem cells, and protects intestinal stem cells against apoptosis both during homeostasis and regeneration in response to ionizing radiation injury, and promotes intestinal tumorigenesis through regulation of multiple signaling pathways.
Signalling that maintains rapid translation elongation in KRAS-mutant colorectal cancer models can be targeted by mutation of the ribosomal protein RPL24 to suppress tumour proliferation.
Ellen N Elliott, Karyn L Sheaffer, Klaus H Kaestner
The maintenance methyltransferase Dnmt1 and the de novo methyltransferase Dnmt3b cooperate to maintain DNA methylation and genomic stability in the adult intestinal epithelium.
Human colonic organoid monolayers self organize into regularly spaced stem and differentiated cell compartments, which are maintained by waves of ERK activity originating from extruded/dying cells.
