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

AI Article Synopsis

  • Maintaining a balance between self-renewal and differentiation is essential for adult stem cells, and the epigenetic factors involved in this process are not yet well understood.
  • Research shows that the Polycomb Repressive Complex 2 (PRC2) is crucial for keeping intestinal stem cell (ISC) levels stable in female fruit flies (Drosophila melanogaster).
  • When PRC2 activity is disrupted, it leads to a loss of stem cell characteristics and premature differentiation of stem cells into mature cells, implicating the microRNA miR-8 and Notch signaling in this regulatory process, which is vital for maintaining intestinal health.*

Article 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10907375PMC
http://dx.doi.org/10.1038/s41467-024-46119-9DOI Listing

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