PT  - JOURNAL ARTICLE
AU  - Vasilia Tamamouna
AU  - Myrofora Panagi
AU  - Andria Theophanous
AU  - Maria Demosthenous
AU  - Maria Michail
AU  - Markella Papadopoulou
AU  - Savvas Teloni
AU  - Chrysoula Pitsouli
AU  - Yiorgos Apidianakis
TI  - Intertwined trade-offs coordinate <em>Drosophila</em> midgut mitosis vs. endoreplication and host defense vs. dysplasia
AID  - 10.1101/615104
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 615104
4099  - http://biorxiv.org/content/early/2019/04/20/615104.short
4100  - http://biorxiv.org/content/early/2019/04/20/615104.full
AB  - Inflammatory signaling supports host defense against infection, not only through immune cells, but also via regeneration of damaged tissue. Heightened regeneration, nevertheless, predisposes for all types of cancer and thus a trade-off exists between regeneration capacity and long-term tissue homeostasis. Here, we study the role of tissue-intrinsic regenerative inflammatory signaling in stem cell mitosis of the adult Drosophila midgut at the baseline and the infected state and its impact on intestinal host defense to infection and stem cell-mediated dysplasia. Through a quantitative genetics screen we find that stem cell mitosis is positively linked with the expression of eiger, Delta, upd3 and vein in the midgut, as well as with dysplasia and host defense, but negatively with enterocyte endoreplication. We provide evidence that intertwined trade-offs fine-tune midgut homeostasis, according to which stem cell mitosis through cyclin E in stem cells promotes the optimal host defense to infection, unless dysplasia ensues. However, cyclin E in enteroblasts promotes enterocyte endoreplication and counterbalances stem cell mitosis and dysplasia, providing an alternative but less efficient mechanism to support host defense.