Coordinated repression of pro-differentiation genes via P-bodies and transcription maintains Drosophila intestinal stem cell identity

The role of processing bodies (P-bodies), key sites of post-transcriptional control, in adult stem cells remains poorly understood. Here, we report that adult Drosophila intestinal stem cells, but not surrounding differentiated cells such as absorptive enterocytes (ECs), harbor P-bodies that contain Drosophila orthologs of mammalian P-body components DDX6, EDC3, EDC4, and LSM14A/B. A targeted RNAi screen in intestinal progenitor cells identified 39 previously known and 64 novel P-body regulators, including Patr-1, a gene necessary for P-body assembly. Loss of Patr-1-dependent P-bodies leads to a loss of stem cells that is associated with inappropriate expression of EC-fate gene nubbin. Transcriptomic analysis of progenitor cells identifies a cadre of such weakly transcribed pro-differentiation transcripts that are elevated after P-body loss. Altogether, this study identifies a P-body-dependent repression activity that coordinates with known transcriptional repression programs to maintain a population of in vivo stem cells in a state primed for differentiation. [Display omitted] •Intestinal progenitors contain constitutive, ultrastructurally organized P-bodies•P-body regulator Patr-1 is required for intestinal progenitor cell maintenance•Enterocyte gene nub is weakly transcribed, but not translated, in progenitors•P-bodies repress enterocyte gene expression to promote stem cell maintenance How stem cells are maintained in adult tissues is a fundamental question. In a new study, Buddika et al. show that Drosophila intestinal stem cells contain P-bodies that repress the expression of weakly transcribed pro-differentiation genes to repress precocious differentiation and thereby ensure the maintenance of this cell.