id author title date pages extension mime words sentences flesch summary cache txt cord-103071-6cgih8o9 Mead, Benjamin E. High-throughput organoid screening enables engineering of intestinal epithelial composition 2020-04-28 .txt text/plain 12408 655 50 Strikingly, in our screen we identify inhibitors of the nuclear exporter Xpo1 modulate stem cell fate commitment by inducing a pan-epithelial stress response combined with an interruption of mitogen signaling in cycling intestinal progenitors, thereby significantly increasing the abundance of Paneth cells independent of known WNT and Notch differentiation cues. Administration of KPT-330 below 160 nM for 6 days (NB higher concentrations proved toxic in primary screening) showed LYZ secretion increasing in a dose-dependent manner, with 160 nM of KPT-330 as the most effective dose among tested concentrations KPT-330 is a selective inhibitor of nuclear export (SINE); these molecules act by suppressing the Xpo1-regulated nuclear export of multiple proteins and mRNAs from the nucleus to the cytoplasm -including genes involved in stem cell maintenance and differentiation as well as inflammatory stress response (Sendino et al., 2018) . ./cache/cord-103071-6cgih8o9.txt ./txt/cord-103071-6cgih8o9.txt