A tumor-suppressive role of the PRC1 Polycomb epigenetic complex in the maintenance of adult Drosophila intestinal stem cell identity
Chromatin modulators, like Polycomb group proteins, are key epigenetic regulators of gene expression and are frequently mutated in cancers. In adult stem cells, epigenetic regulation maintains their identity and controls their differentiation during homeostasis or aging, but its direct role in tumorigenesis remains unclear. Here we developed a novel tumor model in Drosophila by exploring the function of Polycomb Repressive Complex 1 (PRC1) in adult intestinal stem cells (ISCs). Disrupting core PRC1 components in ISCs induces the formation of small cell clusters devoid of intestinal markers, a novel phenotype linked to premature mortality under stress. These clusters exhibit neoplastic characteristics such as overproliferation and continuous growth in serial transplantations, leading to their designation as tumor-initiating intestinal cells (TIICs). While JAK/STAT signaling contributes to TIIC growth, the NF-κB-related Toll/Imd immune pathways restrict their expansion independently of cell death. Altogether, our results highlight PRC1 as an epigenetic tumor suppressor in adult stem cells.
Authors
- Anne-Marie Martinez
- Armel Gallet (ORCID: https://orcid.org/0000-0002-2054-4780)
- Raphaël Rousset (ORCID: https://orcid.org/0000-0002-4999-403X)
- Aurélia Joly (ORCID: https://orcid.org/0000-0003-3055-2693)
- Julie Soltys
- Corinne Rancurel (ORCID: https://orcid.org/0000-0001-9355-5491)
- Rihab Loudhaief (ORCID: https://orcid.org/0000-0002-3987-6371)
- Edan Foley (27365)
- Ana-Maria Popmihaylova (ORCID: https://orcid.org/0000-0001-5081-4326)
Institutions
- Centre National de la Recherche Scientifique (FR)
- University of Alberta (CA)
- Université de Montpellier (FR)
- Université Côte d'Azur (FR)
- Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (FR)
- Institut Sophia Agrobiotech (FR)
- Institut de Génétique Humaine (FR)
Publication Details
- Journal
- PLoS Genetics
- Published
- 2026-07-17
- DOI
- https://doi.org/10.1371/journal.pgen.1012226
- Primary Topic
- Epigenetics and DNA Methylation
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- University of Alberta
- Agence Nationale de la Recherche
- Fondation pour la Recherche Médicale
- Fondation ARC pour la Recherche sur le Cancer
- Ligue Contre le Cancer
- Ministère de l'Education Nationale, de l'Enseignement Superieur et de la Recherche
- Ministère de l'Enseignement Supérieur et de la Recherche
- Centre National de la Recherche Scientifique
- Université de Montpellier
- National Institutes of Health
- Canadian Institutes of Health Research
- European Research Council