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...

Full description

Saved in:

Bibliographic Details
Published in:	Current biology Vol. 32; no. 2; pp. 386 - 397.e6
Main Authors:	Buddika, Kasun, Huang, Yi-Ting, Ariyapala, Ishara S., Butrum-Griffith, Alex, Norrell, Sam A., O’Connor, Alex M., Patel, Viraj K., Rector, Samuel A., Slovan, Mark, Sokolowski, Mallory, Kato, Yasuko, Nakamura, Akira, Sokol, Nicholas S.
Format:	Journal Article
Language:	English
Published:	England Elsevier Inc 24-01-2022
Subjects:	Animals Cell Differentiation - genetics Drosophila - genetics Drosophila - metabolism Drosophila Proteins - genetics Drosophila Proteins - metabolism FMRP intestinal stem cells Intestines ISCs Mammals Me31B P-bodies Patr-1 Stem Cells - metabolism stress granules TRAL P-bodies Patr-1 FMRP intestinal stem cells Me31B ISCs stress granules TRAL
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Equal contribution Conceptualization, K.B., and N.S.S.; Methodology, K.B., Y-T.H., I.S.A., and N.S.S.; Investigation and Analysis, K.B., Y-T.H., I.S.A., A.B-G., S.A.N., A.M.O., V.K.P., S.A.R., M.S., and M.S.; Writing – Original Draft, K.B., and N.S.S.; Writing – Review & Editing, K.B., and N.S.S.; Resources, Y.K., A.N., and N.S.S.; Supervision, K.B., and N.S.S.; Project administration: K.B., and N.S.S.; Funding acquisition: N.S.S. Author Contributions
ISSN:	0960-9822 1879-0445
DOI:	10.1016/j.cub.2021.11.032