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Citation
Arnaoutov, A., Lee, H., Plevock Haase, K., Aksenova, V., Jarnik, M., Oliver, B., Serpe, M., Dasso, M. (2020). IRBIT Directs Differentiation of Intestinal Stem Cell Progeny to Maintain Tissue Homeostasis.  iScience 23(3): 100954.
FlyBase ID
FBrf0245221
Publication Type
Research paper
Abstract

The maintenance of the intestinal epithelium is ensured by the controlled proliferation of intestinal stem cells (ISCs) and differentiation of their progeny into various cell types, including enterocytes (ECs) that both mediate nutrient absorption and provide a barrier against pathogens. The signals that regulate transition of proliferative ISCs into differentiated ECs are not fully understood. IRBIT is an evolutionarily conserved protein that regulates ribonucleotide reductase (RNR), an enzyme critical for the generation of DNA precursors. Here, we show that IRBIT expression in ISC progeny within the Drosophila midgut epithelium cells regulates their differentiation via suppression of RNR activity. Disruption of this IRBIT-RNR regulatory circuit causes a premature loss of intestinal tissue integrity. Furthermore, age-related dysplasia can be reversed by suppression of RNR activity in ISC progeny. Collectively, our findings demonstrate a role of the IRBIT-RNR pathway in gut homeostasis.

PubMed ID
PubMed Central ID
PMC7068126 (PMC) (EuropePMC)
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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    iScience
    Title
    iScience
    ISBN/ISSN
    2589-0042
    Data From Reference