The regenerative activity of adult stem cells carries a risk of cancer, particularly in highly renewable tissues. Members of the family of inhibitor of apoptosis proteins (IAPs) inhibit caspases and cell death, and are often deregulated in adult cancers; however, their roles in normal adult tissue homeostasis are unclear. Here, we show that regulation of the number of enterocyte-committed progenitor (enteroblast) cells in the adult Drosophila involves a caspase-mediated physiological apoptosis, which adaptively eliminates excess enteroblast cells produced by intestinal stem cells (ISCs) and, when blocked, can also lead to tumorigenesis. Importantly, we found that Diap1 is expressed by enteroblast cells and that loss and gain of Diap1 led to changes in enteroblast numbers. We also found that antagonistic interplay between Notch and EGFR signalling governs enteroblast life/death decisions via the Klumpfuss/WT1 and Lozenge/RUNX transcription regulators, which also regulate enteroblast differentiation and cell fate plasticity. These data provide new insights into how caspases drive adult tissue renewal and protect against the formation of tumours.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826210 | PMC |
| http://dx.doi.org/10.15252/embj.2018101346 | DOI Listing |
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- Sphingolipids like ceramides play a significant role in high-fat diets and can influence fatty acid oxidation and intestinal stem cell (ISC) proliferation, potentially leading to cancer risk.
- The study manipulated the ceramide synthesis pathway in midgut intestinal cells to observe how changes in enzyme activities impacted cell behavior, revealing significant alterations in ISC proliferation and cell characteristics.
- Findings suggest that increased levels of saturated sphingolipids trigger inflammation in the gut, which in turn stimulates ISC proliferation through specific pro-inflammatory signals.
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