Stem-Cell-Based Tumorigenesis in Adult Drosophila

2017 ◽  
pp. 311-337 ◽  
Author(s):  
S.X. Hou ◽  
S.R. Singh
Keyword(s):  
Stem Cell ◽  
Adult Drosophila

scholarly journals Damage sensing by a Nox-Ask1-MKK3-p38 signaling pathway mediates regeneration in the adult Drosophila midgut

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Parthive H. Patel ◽  
Clothilde Pénalva ◽  
Michael Kardorff ◽  
Marianne Roca ◽  
Bojana Pavlović ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Stem Cell ◽  
Nadph Oxidase ◽  
Bacterial Infection ◽  
Intestinal Stem Cell ◽  
Oxygen Species ◽  
Damage Sensing ◽  
Mechanical Insult ◽  
Adult Drosophila

Abstract Epithelia are exposed to diverse types of stress and damage from pathogens and the environment, and respond by regenerating. Yet, the proximal mechanisms that sense epithelial damage remain poorly understood. Here we report that p38 signaling is activated in adult Drosophila midgut enterocytes in response to diverse stresses including pathogenic bacterial infection and chemical and mechanical insult. Two upstream kinases, Ask1 and Licorne (MKK3), are required for p38 activation following infection, oxidative stress, detergent exposure and wounding. Ask1-p38 signaling in enterocytes is required upon infection to promote full intestinal stem cell (ISC) activation and regeneration, partly through Upd3/Jak-Stat signaling. Furthermore, reactive oxygen species (ROS) produced by the NADPH oxidase Nox in enterocytes, are required for p38 activation in enterocytes following infection or wounding, and for ISC activation upon infection or detergent exposure. We propose that Nox-ROS-Ask1-MKK3-p38 signaling in enterocytes integrates multiple different stresses to induce regeneration.

scholarly journals Regulation of Drosophila Intestinal Stem Cell Maintenance and Proliferation

2015 ◽  
Vol 2 (1) ◽  
pp. 77-84
Author(s):  
Olha Strilbytska
Keyword(s):  
Stem Cell ◽  
Signaling Pathways ◽  
Intestinal Stem Cells ◽  
Stem Cell Maintenance ◽  
Intestinal Integrity ◽  
Proliferation And Differentiation ◽  
Gut Homeostasis ◽  
Multiple Signaling ◽  
Adult Drosophila ◽  
Cell Maintenance

To maintain gut homeostasis intestinal stem cells (ISCs) constantly replace damagedones. This process is conservative from Drosophila to human. Proliferation and differentiation ofISCs in adult Drosophila midgut are regulated by growth factors which are secreted in thesurrounding cells collectively forming ISCs niche. Here I discuss an interaction between ISCs withits niche through conservative signaling pathways. Several evidences on significance ofcooperation between multiple signaling pathways including Notch, Wingless, JAK/STAT, EGFR,Hippo, and insulin signaling for regulation of stem cell maintenance and activity are provided.Further investigation in this area will allow us to understand how proper regulation of ISCsmaintenance and differentiation can assist to ensure intestinal integrity

scholarly journals I-KCKT allows dissection-free RNA profiling of adult Drosophila intestinal progenitor cells

2020 ◽  
Author(s):  
Kasun Buddika ◽  
Jingjing Xu ◽  
Ishara S. Ariyapala ◽  
Nicholas S. Sokol
Keyword(s):  
Stem Cell ◽  
Progenitor Cells ◽  
Protein Interactions ◽  
Cell Biology ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Stem Cell Population ◽  
Binding Motif ◽  
Rna Profiling ◽  
Adult Drosophila

AbstractThe adult Drosophila intestinal epithelium is a model system for stem cell biology, but its utility is limited by current biochemical methods that lack cell type resolution. Here, we describe a new proximity-based profiling method that relies upon a GAL4 driver, termed intestinal-kickout-GAL4 (I-KCKT-GAL4), exclusively expressed in intestinal progenitor cells. This method used UV cross-linked whole animal frozen powder as its starting material to immunoprecipitate the RNA cargoes of transgenic epitope-tagged RNA binding proteins driven by I-KCKT-GAL4. When applied to the general mRNA-binder, poly(A)-binding protein, the RNA profile obtained by this method identified 98.8% of transcripts found after progenitor cell sorting, and had low background noise despite being derived from whole animal lysate. We also mapped the targets of the more selective RNA binder, Fragile Mental Retardation Protein, using enhanced CLIP, and report for the first time its binding motif in Drosophila cells. This method will therefore enable the RNA profiling of wildtype and mutant intestinal progenitor cells from intact flies exposed to normal and altered environments, as well as the identification of RNA-protein interactions critical for stem cell function.Summary StatementWe report a dissection-free method to identify proximity-based RNA-protein interactions in an in vivo stem cell population, enabling molecular analysis of these cells at unprecedented speed and resolution.

scholarly journals Mono-Association with Lactobacillus plantarum Disrupts Intestinal Homeostasis in adult Drosophila

2016 ◽  
Author(s):  
David Fast ◽  
Aashna Duggal ◽  
Edan Foley
Keyword(s):  
Stem Cell ◽  
Cell Division ◽  
Lactobacillus Plantarum ◽  
Intestinal Stem Cells ◽  
Adult Longevity ◽  
Intestinal Homeostasis ◽  
Intestinal Pathology ◽  
Evolutionarily Conserved ◽  
Stem Cell Division ◽  
Adult Drosophila

ABSTRACTThe microbiome of Drosophila promotes intestinal stem cell division through evolutionarily conserved biochemical pathways. As such, axenic flies have lower rates of gut stem cell division than age-matched wild type counterparts. Additionally, flies with a full consortium of symbiotic bacteria are shorter lived than those maintained in the absence of a microbiome. However, we do not know if stem cell division is essential for symbiont-dependent regulation of adult fly lifespan. To determine if individual symbionts cause aging-dependent death in Drosophila, we examined the impacts of common symbionts on host longevity. In this study, we found that mono-association of adult Drosophila with Lactobacillus plantarum, a widely reported fly symbiont, and member of the probiotic Lactobacillus genus, curtails adult longevity relative to germ-free counterparts. However, the effects of plantarum on lifespan were independent of intestinal aging. Instead, we found that association with plantarum causes an extensive intestinal pathology within the host, characterized by loss of intestinal stem cells, impaired epithelial renewal, and a gradual erosion of epithelial integrity. Our study uncovers an unknown aspect of Lactobacillus plantarum-Drosophila interactions, and establishes a simple model to characterize symbiont-dependent disruption of intestinal homeostasis.

scholarly journals Local Control of Intestinal Stem Cell Homeostasis by Enteroendocrine Cells in the Adult Drosophila Midgut

2014 ◽  
Vol 24 (11) ◽  
pp. 1199-1211 ◽  
Author(s):  
Alessandro Scopelliti ◽  
Julia B. Cordero ◽  
Fengqiu Diao ◽  
Karen Strathdee ◽  
Benjamin H. White ◽  
...  
Keyword(s):  
Stem Cell ◽  
Local Control ◽  
Enteroendocrine Cells ◽  
Intestinal Stem Cell ◽  
Cell Homeostasis ◽  
Adult Drosophila

scholarly journals A model for adult organ resizing demonstrates stem cell scaling through a tunable commitment rate

2017 ◽  
Author(s):  
XinXin Du ◽  
Lucy Erin O’Brien ◽  
Ingmar Riedel-Kruse
Keyword(s):  
Stem Cell ◽  
Theoretical Models ◽  
Cell Number ◽  
Cellular Behaviors ◽  
Tissue Space ◽  
Physiological Demands ◽  
Kinetics Of ◽  
Cell Proportion ◽  
Adult Drosophila

AbstractMany adult organs grow or shrink to accommodate different physiological demands. Often, as total cell number changes, stem cell number changes proportionally in a phenomenon called ‘stem cell scaling’. The cellular behaviors that give rise to scaling are unknown. Here we study two complementary theoretical models of the adult Drosophila midgut, a stem cell-based organ with known resizing dynamics. First, we derive a differential equations model of midgut resizing and show that the in vivo kinetics of growth can be recapitulated if the rate of fate commitment depends on the tissue’s stem cell proportion. Second, we develop a twodimensional simulation of the midgut and find that proportion-dependent commitment rate and stem cell scaling can arise phenomenologically from the stem cells’ exploration of physical tissue space during its lifetime. Together, these models provide a biophysical understanding of how stem cell scaling is maintained during organ growth and shrinkage.

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