Ribosome impairment regulates intestinal stem cell identity via ZAKɑ activation

We show that ribosome collisions, induced by Rptor deletion or aminoacid starvation, causes a ZAK alpha mediated identity switch in intestinal stem cells by activating a more fetal-like stem cell signature. This switch also causes changes in metabolic profiles of the cells, which is heavily regulated by RNA translation efficiency of different group of metabolic genes. These observations originate from performing in vitro Riboseq and RNAseq in mouse intestinal organoids, and in vivo Riboseq in Lgr5 expressing intestinal stem cells from WT and Rptor.fl/fl mice. In vitro Ribo-seq and RNAseq in WT-stem cell enriched, WT-stem cell depleted and Rptor fl/fl mouse intestinal organoids. In vitro RNAseq in WT mouse intestinal organoids. In vivo Ribo-seq in Lgr5 expressing intestinal stem cells from WT and Rptor fl/fl mouse.