Coordinated repression of pro-differentiation genes via P-bodies and transcription maintains Drosophila intestinal stem cell identity
Introduction
In this story we describe the identification, structure and function of Processing bodies (P-bodies) in a somatic stem cell population of the Drosophila intestine. This is the third class of cytoplasmic mRNP that I identified in the cytoplasm this exciting cell population. In an earlier story (please see here), we identified the presence of stress granule cores and intestinal progenitor stress granules (IPSGs) which altogether forms the three types of mRNPs in intestinal progenitors.
Highlights
- 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
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.
Further Reading
If you are interested in knowing more about intestinal stem cells P-bodies and their function, please read the full story that is available here.
Cite this work
Buddika K, Huang YT, Ariyapala IS, Butrum-Griffith A, Norrell SA, O’Connor AM, Patel VK, Rector SA, Slovan M, Sokolowski M, Kato Y, Nakamura A, Sokol NS. 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. PMID: 34875230; PMCID: PMC8792327.