IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-46119-9.html
   My bibliography  Save this article

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

Author

Listed:
  • 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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-46119-9
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-46119-9?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    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. 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.
    3. 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.
    4. 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.
    5. 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.
    6. 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.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Xingting Guo & Chenhui Wang & Yongchao Zhang & Ruxue Wei & Rongwen Xi, 2024. "Cell-fate conversion of intestinal cells in adult Drosophila midgut by depleting a single transcription factor," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. Kathyani Parasram & Amy Zuccato & Minjeong Shin & Reegan Willms & Brian DeVeale & Edan Foley & Phillip Karpowicz, 2024. "The emergence of circadian timekeeping in the intestine," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    3. Christian F. Christensen & Quentin Laurichesse & Rihab Loudhaief & Julien Colombani & Ditte S. Andersen, 2024. "Drosophila activins adapt gut size to food intake and promote regenerative growth," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    4. Daniel Jun-Kit Hu & Jina Yun & Justin Elstrott & Heinrich Jasper, 2021. "Non-canonical Wnt signaling promotes directed migration of intestinal stem cells to sites of injury," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    5. Seungjae Lee & Yen-Chung Chen & Austin E. Gillen & J. Matthew Taliaferro & Bart Deplancke & Hongjie Li & Eric C. Lai, 2022. "Diverse cell-specific patterns of alternative polyadenylation in Drosophila," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    6. Xingting Guo & Yongchao Zhang & Huanwei Huang & Rongwen Xi, 2022. "A hierarchical transcription factor cascade regulates enteroendocrine cell diversity and plasticity in Drosophila," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    7. Michelle Dietzen & Haoran Zhai & Olivia Lucas & Oriol Pich & Christopher Barrington & Wei-Ting Lu & Sophia Ward & Yanping Guo & Robert E. Hynds & Simone Zaccaria & Charles Swanton & Nicholas McGranaha, 2024. "Replication timing alterations are associated with mutation acquisition during breast and lung cancer evolution," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    8. Enas E. Nasr & Zeinab Z. Khater & Martina Zelenakova & Zuzana Vranayova & Mohamed Abu-Hashim, 2020. "Soil Physicochemical Properties, Metal Deposition, and Ultrastructural Midgut Changes in Ground Beetles, Calosoma chlorostictum, under Agricultural Pollution," Sustainability, MDPI, vol. 12(12), pages 1-17, June.
    9. Buki Kwon & Mervin M. Fansler & Neil D. Patel & Jihye Lee & Weirui Ma & Christine Mayr, 2022. "Enhancers regulate 3′ end processing activity to control expression of alternative 3′UTR isoforms," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    10. Alexandra D’Oto & Jie Fang & Hongjian Jin & Beisi Xu & Shivendra Singh & Anoushka Mullasseril & Victoria Jones & Ahmed Abu-Zaid & Xinyu Buttlar & Bailey Cooke & Dongli Hu & Jason Shohet & Andrew J. Mu, 2021. "KDM6B promotes activation of the oncogenic CDK4/6-pRB-E2F pathway by maintaining enhancer activity in MYCN-amplified neuroblastoma," Nature Communications, Nature, vol. 12(1), pages 1-19, December.
    11. Yue Li & Tianfeng Lu & Pengzhen Dong & Jian Chen & Qiang Zhao & Yuying Wang & Tianheng Xiao & Honggang Wu & Quanyi Zhao & Hai Huang, 2024. "A single-cell atlas of Drosophila trachea reveals glycosylation-mediated Notch signaling in cell fate specification," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    12. Junjun Gao & Song Zhang & Pan Deng & Zhigang Wu & Bruno Lemaitre & Zongzhao Zhai & Zheng Guo, 2024. "Dietary L-Glu sensing by enteroendocrine cells adjusts food intake via modulating gut PYY/NPF secretion," Nature Communications, Nature, vol. 15(1), pages 1-22, December.
    13. Agnes Banreti & Shayon Bhattacharya & Frank Wien & Koichi Matsuo & Matthieu Réfrégiers & Cornelia Meinert & Uwe Meierhenrich & Bruno Hudry & Damien Thompson & Stéphane Noselli, 2022. "Biological effects of the loss of homochirality in a multicellular organism," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    14. Lianjun Zhang & Le Xuan Truong Nguyen & Ying-Chieh Chen & Dijiong Wu & Guerry J. Cook & Dinh Hoa Hoang & Casey J. Brewer & Xin He & Haojie Dong & Shu Li & Man Li & Dandan Zhao & Jing Qi & Wei-Kai Hua , 2021. "Targeting miR-126 in inv(16) acute myeloid leukemia inhibits leukemia development and leukemia stem cell maintenance," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    15. Guang Shi & D. Thirumalai, 2023. "A maximum-entropy model to predict 3D structural ensembles of chromatin from pairwise distances with applications to interphase chromosomes and structural variants," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    16. Jason P. Wray & Elitza M. Deltcheva & Charlotta Boiers & Simon Е Richardson & Jyoti Bikram Chhetri & John Brown & Sladjana Gagrica & Yanping Guo & Anuradha Illendula & Joost H. A. Martens & Hendrik G., 2022. "Regulome analysis in B-acute lymphoblastic leukemia exposes Core Binding Factor addiction as a therapeutic vulnerability," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    17. Hannah L. Harris & Huiya Gu & Moshe Olshansky & Ailun Wang & Irene Farabella & Yossi Eliaz & Achyuth Kalluchi & Akshay Krishna & Mozes Jacobs & Gesine Cauer & Melanie Pham & Suhas S. P. Rao & Olga Dud, 2023. "Chromatin alternates between A and B compartments at kilobase scale for subgenic organization," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    18. Jiapei Yuan & Yang Tong & Le Wang & Xiaoxiao Yang & Xiaochuan Liu & Meng Shu & Zekun Li & Wen Jin & Chenchen Guan & Yuting Wang & Qiang Zhang & Yang Yang, 2024. "A compendium of genetic variations associated with promoter usage across 49 human tissues," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    19. Natasha Hui Jin Ng & Soumita Ghosh & Chek Mei Bok & Carmen Ching & Blaise Su Jun Low & Juin Ting Chen & Euodia Lim & María Clara Miserendino & Yaw Sing Tan & Shawn Hoon & Adrian Kee Keong Teo, 2024. "HNF4A and HNF1A exhibit tissue specific target gene regulation in pancreatic beta cells and hepatocytes," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    20. Zachary T. Spencer & Victoria H. Ng & Hassina Benchabane & Ghalia Saad Siddiqui & Deepesh Duwadi & Ben Maines & Jamal M. Bryant & Anna Schwarzkopf & Kai Yuan & Sara N. Kassel & Anant Mishra & Ashley P, 2023. "The USP46 deubiquitylase complex increases Wingless/Wnt signaling strength by stabilizing Arrow/LRP6," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46119-9. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.