Evidence of two types of balance between stem cell mitosis and enterocyte nucleus growth in the Drosophila midgut

Abstract

Systemic and stem cell niche-emanating cytokines and growth factors can promote regeneration, through mitosis. High mitosis, however, predisposes for all types of cancer and, thus, a trade-off exists between regeneration capacity and tissue homeostasis. Here, we study the role of tissue-intrinsic regenerative signaling in stem cell mitosis of adult Drosophila midgut of different genetic backgrounds. We provide evidence of two naturally occurring types of balance between mitosis and enterocyte nucleus growth: one based mostly on stem cell mitosis producing new cells and the other based mostly on the degree of young enterocyte nucleus size increase. Mitosis promotes intestinal host defense to infection, but predisposes for dysplasia in the form of stem cell-like clusters. Enterocyte nucleus growth also promotes host defense, without the drawback of promoting dysplasia. Through quantitative genetics, we identified eiger as an autocrine and paracrine inducer of stem cell mitosis. eiger expression in immature epithelial cells tilts the balance towards mitosis and dysplasia via a positive-feedback loop of highly mitotic stem cells sustaining more small nucleus enterocytes, which in turn supply more Eiger.

Multiscale analysis reveals that diet-dependent midgut plasticity emerges from alterations in both stem cell niche coupling and enterocyte size

“…This suggests that proliferation and cell size need to be properly coordinated to lead to normal changes in organ size. This hypothesis agrees with a recent study demonstrating a balance between stem cell mitosis and enterocyte nucleus growth in the midgut of Drosophila (Tamamouna et al, 2020). Additionally, we cannot discount a role for enteroblasts (EBs) in organ regulation.…”

The Role of Citrate Transporter INDY in Metabolism and Stem Cell Homeostasis

“…The influence of genetic background on longevity is well-known, as the effect of Indy reduction on longevity in Drosophila has been examined and documented in varied genetic backgrounds listed in the above mentioned studies [ 1 , 13 , 16 , 22 ]. Genetic background has been shown to impact quantitative physiological traits measured as markers of aging as well as intestinal stem cell proliferation in Drosophila [ 28 , 29 ]. Use of a diet similar to calorie restriction (CR) may affect longevity of Indy alleles in the Toivonen et al study [ 22 , 27 ].…”

The amino acid transporter CG1139 is required for retrograde transport and fast recovery of gut enterocytes after Serratia marcescens intestinal infection

“…As TOR signaling contributes to this adaptation, enterocyte growth is implicitly thought to be a cell-autonomous event. Indeed, the mechanisms behind the control of enterocyte growth and regulation of size have gain interest on the field (Xiang et al, 2017;Wen et al, 2017;Tamamouna and Panagi et al, 2020) The enterocyte cytoplasmic purge provides a unique setting in which the regrowth of enterocytes following the extrusion of their apical cytoplasm is uncoupled from ISC proliferation (Lee et al, 2016). Here, we document that the regrowth of enterocytes depends solely on an inversion of metabolic fluxes from the organism to the gut.…”