Tissue homeostasis requires a balance of mitotic cell fate choice between stem cell maintenance and the production of progenitors that enter a differentiated state. In the intestinal crypt, the position of the cell, not the segregation of fate determinants, appears to regulate cell fate. Homeostasis is perturbed in mutants for tumour suppressor genes, such as adenomatous polyposis coli (Apc), as cells increasingly colonise proliferative niches. However, the mechanism that controls the position of intestinal cells in the epithelium is poorly understood. In this issue (p. 3862), Inke Näthke and colleagues use intestinal organoids to study daughter cell positioning. When epithelial cells enter mitosis, their nuclei migrate apically in the epithelial layer; cells divide and remain either adjacent to each other or separate during basal movement. This separation occurs ∼30% in wild type, and the authors show through computational modelling that it yields more heterogenous pairs than the adjacent placement of cells, which enhances divergent daughter cell fate. Importantly, in epithelial cells mutant for Apc this separation is lost, which−together with the decreased migration of Apc-mutant cells−promotes the retention of daughter cells in a proliferative niche. Taken together, this study provides evidence that intestinal epithelial cells control niche access through post-mitotic separation.
