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Polycomb-mediated silencing of miR-8 is required for maintenance of intestinal stemness in Drosophila melanogaster

Author

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  • Zoe Veneti

    (Foundation of Research & Technology Hellas
    University of Crete)

  • Virginia Fasoulaki

    (Foundation of Research & Technology Hellas
    University of Crete)

  • Nikolaos Kalavros

    (Beth Israel Deaconess Medical Center
    Broad Institute of MIT and Harvard)

  • Ioannis S. Vlachos

    (Beth Israel Deaconess Medical Center
    Broad Institute of MIT and Harvard
    Harvard Medical School)

  • Christos Delidakis

    (Foundation of Research & Technology Hellas
    University of Crete)

  • Aristides G. Eliopoulos

    (National and Kapodistrian University of Athens
    Biomedical Research Foundation of the Academy of Athens)

Abstract

Balancing maintenance of self-renewal and differentiation is a key property of adult stem cells. The epigenetic mechanisms controlling this balance remain largely unknown. Herein, we report that the Polycomb Repressive Complex 2 (PRC2) is required for maintenance of the intestinal stem cell (ISC) pool in the adult female Drosophila melanogaster. We show that loss of PRC2 activity in ISCs by RNAi-mediated knockdown or genetic ablation of the enzymatic subunit Enhancer of zeste, E(z), results in loss of stemness and precocious differentiation of enteroblasts to enterocytes. Mechanistically, we have identified the microRNA miR-8 as a critical target of E(z)/PRC2-mediated tri-methylation of histone H3 at Lys27 (H3K27me3) and uncovered a dynamic relationship between E(z), miR-8 and Notch signaling in controlling stemness versus differentiation of ISCs. Collectively, these findings uncover a hitherto unrecognized epigenetic layer in the regulation of stem cell specification that safeguards intestinal homeostasis.

Suggested Citation

  • Zoe Veneti & Virginia Fasoulaki & Nikolaos Kalavros & Ioannis S. Vlachos & Christos Delidakis & Aristides G. Eliopoulos, 2024. "Polycomb-mediated silencing of miR-8 is required for maintenance of intestinal stemness in Drosophila melanogaster," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46119-9
    DOI: 10.1038/s41467-024-46119-9
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    References listed on IDEAS

    as
    1. Craig A. Micchelli & Norbert Perrimon, 2006. "Evidence that stem cells reside in the adult Drosophila midgut epithelium," Nature, Nature, vol. 439(7075), pages 475-479, January.
    2. Panagiotis Ntziachristos & Aristotelis Tsirigos & G. Grant Welstead & Thomas Trimarchi & Sofia Bakogianni & Luyao Xu & Evangelia Loizou & Linda Holmfeldt & Alexandros Strikoudis & Bryan King & Jasper , 2014. "Contrasting roles of histone 3 lysine 27 demethylases in acute lymphoblastic leukaemia," Nature, Nature, vol. 514(7523), pages 513-517, October.
    3. Jerome Korzelius & Sina Azami & Tal Ronnen-Oron & Philipp Koch & Maik Baldauf & Elke Meier & Imilce A. Rodriguez-Fernandez & Marco Groth & Pedro Sousa-Victor & Heinrich Jasper, 2019. "The WT1-like transcription factor Klumpfuss maintains lineage commitment of enterocyte progenitors in the Drosophila intestine," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    4. Yongli Shan & Yanqi Zhang & Yuan Zhao & Tianyu Wang & Jingyuan Zhang & Jiao Yao & Ning Ma & Zechuan Liang & Wenhao Huang & Ke Huang & Tian Zhang & Zhenghui Su & Qianyu Chen & Yanling Zhu & Chuman Wu &, 2020. "JMJD3 and UTX determine fidelity and lineage specification of human neural progenitor cells," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
    5. Benjamin Ohlstein & Allan Spradling, 2006. "The adult Drosophila posterior midgut is maintained by pluripotent stem cells," Nature, Nature, vol. 439(7075), pages 470-474, January.
    6. Jing Zhang & Donghoon Lee & Vineet Dhiman & Peng Jiang & Jie Xu & Patrick McGillivray & Hongbo Yang & Jason Liu & William Meyerson & Declan Clarke & Mengting Gu & Shantao Li & Shaoke Lou & Jinrui Xu &, 2020. "An integrative ENCODE resource for cancer genomics," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
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