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

Curr Biol. 2022 Jan 24;32(2):386-397.e6. doi: 10.1016/j.cub.2021.11.032. Epub 2021 Dec 6.

Abstract

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.

Keywords: FMRP; ISCs; Me31B; P-bodies; Patr-1; TRAL; intestinal stem cells; stress granules.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Drosophila Proteins* / genetics
  • Drosophila Proteins* / metabolism
  • Drosophila* / genetics
  • Drosophila* / metabolism
  • Intestines
  • Mammals
  • Stem Cells / metabolism

Substances

  • Drosophila Proteins