Adult stem cells play crucial roles in tissue homeostasis, giving rise to both new stem cells and differentiating daughter cells. The generation of these two cell types often involves the asymmetric distribution of cell fate determinants, but how these factors are partitioned asymmetrically has been unclear. Now (p. ), Chrystelle Montagne and Marcos Gonzalez-Gaitan reveal a role for Sara endosomes in the asymmetric division of Drosophila intestinal stem cells (ISCs). Using live imaging of the adult fly midgut, the researchers first show that Sara endosomes, which are characterised by the localisation of the endosomal protein Sara, are unequally partitioned during ISC divisions, being preferentially targeted to the presumptive differentiating cell. They further examine the distribution of Notch and Delta, which have been implicated in regulating ISC fate, and show that both Notch and Delta traffic through Sara endosomes and, accordingly, are also asymmetrically dispatched to the differentiating cell. Importantly, they demonstrate that midgut homeostasis is perturbed in Sara mutants; the number of ISCs in the midgut is significantly higher in Sara mutants than in controls, indicating that Sara endosomes play a central role in assigning ISC fate. These, together with other findings, uncover a cell-intrinsic endosomal-based mechanism for regulating cell fate and asymmetric cell division.
