Intestinal Stem Cells

Apidianakis, Yiorgos; Tamamouna, Vasilia; Teloni, Savvas; Pitsouli, Chrysoula

doi:10.1016/bs.aiip.2017.03.002

Cited by 8 publications

(4 citation statements)

References 165 publications

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“…We investigated the regulation of turnover in the midgut epithelium of adult Drosophila 5 (Extended Data Fig. 1a–e).…”

Section: Main Textmentioning

confidence: 99%

“…However, the mechanistic basis of this equilibrium is unknown. Using the adult Drosophila intestine 5 , we find that robustly precise turnover arises through a coupling mechanism in which enterocyte apoptosis breaks feedback inhibition of stem cell divisions. Healthy enterocytes inhibit stem cell division through E-cadherin, which prevents secretion of mitogenic EGFs by repressing transcription of the EGF maturation factor rhomboid .…”

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confidence: 99%

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Feedback regulation of steady-state epithelial turnover and organ size

Liang

Balachandra

Ngo

et al. 2017

Nature

143

153

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Epithelial organs undergo steady-state turnover throughout adult life, with old cells being continually replaced by the progeny of stem cell divisions1. To avoid hyperplasia or atrophy, organ turnover demands strict equilibration of cell production and loss2–4. However, the mechanistic basis of this equilibrium is unknown. Using the adult Drosophila intestine5, we find that robustly precise turnover arises through a coupling mechanism in which enterocyte apoptosis breaks feedback inhibition of stem cell divisions. Healthy enterocytes inhibit stem cell division through E-cadherin, which prevents secretion of mitogenic EGFs by repressing transcription of the EGF maturation factor rhomboid. Individual apoptotic enterocytes promote divisions by loss of E-cadherin, which releases cadherin-associated β-catenin/Armadillo and p120-catenin to induce rhomboid. Induction of rhomboid in the dying enterocyte triggers EGFR activation in stem cells within a discrete radius. When we block apoptosis, E-cadherin-controlled feedback suppresses divisions, and the organ retains the same number of cells. When we disrupt feedback, apoptosis and divisions are uncoupled, and the organ develops either hyperplasia or atrophy. Altogether, our work demonstrates that robust cellular balance hinges on the obligate coupling of divisions to apoptosis, which limits the proliferative potential of a stem cell to the precise time and place that a replacement cell is needed. In this manner, localized cell-cell communication gives rise to tissue-level homeostatic equilibrium and constant organ size.

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“…We investigated the regulation of turnover in the midgut epithelium of adult Drosophila 5 (Extended Data Fig. 1a–e).…”

Section: Main Textmentioning

confidence: 99%

mentioning

confidence: 99%

Feedback regulation of steady-state epithelial turnover and organ size

Liang

Balachandra

Ngo

et al. 2017

Nature

143

153

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“…The Drosophila midgut is physiologically equivalent to the vertebrate stomach and small intestine. As in vertebrate intestines, stem cells in the fly midgut continuously divide to replenish terminally differentiated epithelial cells that form the intestinal barrier [13]. Although current live-imaging methods capture single divisions [12], their �16-h timescales are insufficient to track multiple divisions of the same stem cell or to monitor differentiation of new progeny.…”

Section: Resultsmentioning

confidence: 99%

Bellymount enables longitudinal, intravital imaging of abdominal organs and the gut microbiota in adult Drosophila

Koyama

Aranda-Díaz

et al. 2020

PLoS Biol

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Cell-and tissue-level processes often occur across days or weeks, but few imaging methods can capture such long timescales. Here, we describe Bellymount, a simple, noninvasive method for longitudinal imaging of the Drosophila abdomen at subcellular resolution. Bellymounted animals remain live and intact, so the same individual can be imaged serially to yield vivid time series of multiday processes. This feature opens the door to longitudinal studies of Drosophila internal organs in their native context. Exploiting Bellymount's capabilities, we track intestinal stem cell lineages and gut microbial colonization in single animals, revealing spatiotemporal dynamics undetectable by previously available methods.

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“…The Drosophila adult midgut has emerged as an excellent system to study stem cell regeneration in response to chemical stress, infection, aging, as well as tissue communication 17–20 . The endoderm-derived midgut is an apicobasally polarized epithelium comprised of intestinal stem cells (ISCs), and their progeny, the transient enteroblasts (EBs) and pre-enteroendocrine cells (pre-EEs), which differentiate to lumen-facing absorptive enterocytes (ECs) and secretory enteroendocrine cells (EEs), respectively 21–23 .…”

Section: Introductionmentioning

confidence: 99%

Remodeling of oxygen-transporting tracheoles drives intestinal regeneration and tumorigenesis

Tamamouna

Petersson

et al. 2021

Preprint

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The Drosophila tracheal system, as the functional equivalent of mammalian blood vessels, responds to hypoxia and transports oxygen throughout the body. Although the signaling pathways involved in tracheal development and the hypoxic response are well-studied, how adult tracheae interact with their target tissues is largely unknown. Here we show that the tracheae that serve the adult intestine are dynamic and respond to enteric infection, oxidative agents, and the development of gut tumors with increased terminal branching. Increased tracheation is necessary for efficient damage-induced intestinal stem cell (ISC)-mediated midgut regeneration and sufficient to drive ISC proliferation in the absence of damage. Gut damage or tumors induce Hif-1α/Sima, which, in turn, stimulates tracheole branching via the FGF(Brachless/Bnl)/FGFR(Breathless/Btl) signaling cascade. Bnl/Btl signaling is required both in the intestinal epithelium and the tracheal system for efficient damage-induced tracheal remodeling and ISC proliferation. We show that chemical or Pseudomonas-generated ROS directly affect the trachea and are necessary for branching and intestinal regeneration. Similarly, tracheole branching and the resulting increase in oxygen supply are essential for tumor growth in the midgut. Thus, we have identified a novel mechanism of visceral tracheal-intestinal tissue communication, whereby oxidative damage and tumors induce neo-tracheogenesis in adult Drosophila. This process is reminiscent of cancer-induced neo-angiogenesis in mammals.

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Intestinal Stem Cells

Cited by 8 publications

References 165 publications

Feedback regulation of steady-state epithelial turnover and organ size

Feedback regulation of steady-state epithelial turnover and organ size

Bellymount enables longitudinal, intravital imaging of abdominal organs and the gut microbiota in adult Drosophila

Remodeling of oxygen-transporting tracheoles drives intestinal regeneration and tumorigenesis

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