Vasopressin regulates uptake of exosomes by kidney collecting duct cells

tumour settings. In addition to regulating tumour cell viability, BET inhibitors are also associatedwith gastrointestinal toxicity, though the molecular and cellular mechanisms behind this toxicity have yet to be elucidated. We have found that BET inhibitors induce a dose-limiting duodenal villous atrophy in vivo, accompanied by inappetance and body weight loss. Ex-vivo cultures of intestinal organoids confirm that villous atrophy occurs withmultiple chemical classes of BET domain inhibitors and that their toxicity is driven by their primary pharmacology. Intriguingly, the intestinal atrophy occurs in the absence of a proliferative block, and in the presence of cMyc, suggesting that the intestinal effects are not mediated by cMyc inhibition as may have been assumed. We find instead that BET domain inhibitors induce a rapid loss of intestinal stem cells, suggesting that it is a loss of stem-cell self renewal leading to crypt loss and dose-limiting duodenal toxicity.