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https://www.readbyqxmd.com/read/28834743/constitutive-immune-activity-promotes-tumorigenesis-in-drosophila-intestinal-progenitor%C3%A2-cells
#1
Kristina Petkau, Meghan Ferguson, Silvia Guntermann, Edan Foley
Gut innate immune defenses control bacterial populations and protect the host interior from invasion. Although excess intestinal immune activity frequently promotes inflammatory illnesses, we know little about the consequences of chronic innate immune activity exclusively in endodermal gut cells of an otherwise normal animal. To address this question, we examined the consequences of persistent inflammatory signals in adult fly intestinal progenitor cells. We found that constitutive immune activity disrupts expression of homeostatic regulators such as Notch pathway components and induces hyperplasia throughout the gut...
August 22, 2017: Cell Reports
https://www.readbyqxmd.com/read/28637464/kaiso-differentially-regulates-components-of-the-notch-signaling-pathway-in-intestinal-cells
#2
Shaiya C Robinson, Kristina Klobucar, Christina C Pierre, Amna Ansari, Svetlana Zhenilo, Egor Prokhortchouk, Juliet M Daniel
BACKGROUND: In mammalian intestines, Notch signaling plays a critical role in mediating cell fate decisions; it promotes the absorptive (or enterocyte) cell fate, while concomitantly inhibiting the secretory cell fate (i.e. goblet, Paneth and enteroendocrine cells). We recently reported that intestinal-specific Kaiso overexpressing mice (Kaiso (Tg) ) exhibited chronic intestinal inflammation and had increased numbers of all three secretory cell types, hinting that Kaiso might regulate Notch signaling in the gut...
June 21, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/28621429/the-sumo-targeted-ubiquitin-ligase-dgrn-is-essential-for-drosophila-innate-immunity
#3
Bella Koltun, Eliza Shackelford, François Bonnay, Nicolas Matt, Jean Marc Reichhart, Amir Orian
The ability of metazoans to combat pathogenic infection involves both systemic and local responses to the invading pathogens. Ubiquitin and SUMO pathways molecularly regulate the response to infection, immune signaling and gene expression. Here, we report that Degringolade (Dgrn, CG10981), a SUMO-targeted ubiquitin ligase connecting the two pathways, is essential for the innate immunity response in Drosophila. dgrn(DK) null and heterozygous mutant adult flies are severely immune-compromised and succumb rapidly to both pathogenic bacteria and fungi infections...
2017: International Journal of Developmental Biology
https://www.readbyqxmd.com/read/28336548/nutrient-sensing-by-absorptive-and-secretory-progenies-of-small-intestinal-stem-cells
#4
Kunihiro Kishida, Sarah C Pearce, Shiyan Yu, Nan Gao, Ronaldo P Ferraris
Nutrient sensing triggers responses by the gut-brain axis modulating hormone release, feeding behavior and metabolism that become dysregulated in metabolic syndrome and some cancers. Except for absorptive enterocytes and secretory enteroendocrine cells, the ability of many intestinal cell types to sense nutrients is still unknown; hence we hypothesized that progenitor stem cells (intestinal stem cells, ISC) possess nutrient sensing ability inherited by progenies during differentiation. We directed via modulators of Wnt and Notch signaling differentiation of precursor mouse intestinal crypts into specialized organoids each containing ISC, enterocyte, goblet, or Paneth cells at relative proportions much higher than in situ as determined by mRNA expression and immunocytochemistry of cell type biomarkers...
June 1, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28250160/glucose-dependent-insulinotropic-polypeptide-receptor-deficiency-leads-to-impaired-bone-marrow-hematopoiesis
#5
Fernanda Dana Mantelmacher, Sigal Fishman, Keren Cohen, Metsada Pasmanik Chor, Yuichiro Yamada, Isabel Zvibel, Chen Varol
The bone marrow (BM) contains controlled specialized microenvironments, or niches, that regulate the quiescence, proliferation, and differentiation of hematopoietic stem and progenitor cells (HSPC). The glucose-dependent insulinotropic polypeptide (GIP) is a gut-derived incretin hormone that mediates postprandial insulin secretion and has anabolic effects on adipose tissue. Previous studies demonstrated altered bone microarchitecture in mice deficient for GIP receptor (Gipr(-/-) ), as well as the expression of high-affinity GIP receptor by distinct cells constructing the BM HSPC niche...
April 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28086833/delta-like-4-notch-signaling-promotes-apc-min-tumor-initiation-through-angiogenic-and-non-angiogenic-related-mechanisms
#6
Marina Badenes, Alexandre Trindade, Hugo Pissarra, Luís Lopes-da-Costa, António Duarte
BACKGROUND: Delta like 4 (Dll4)/Notch signaling is a key regulator of tumor angiogenesis. Additionally, the role of Dll4 has been studied on tumor stem cells. However, as these cells are implicated in tumor angiogenesis, it is conceivable that the effect of Dll4 on these cells may be a consequence of its angiogenic function. Our aim was to evaluate the expression and dissect the functions of Dll4 in the Apc (Min/+) model of colorectal cancer. METHODS: We evaluated the protein expression pattern of Dll4 and other Notch members in the Apc (Min/+) tumors relatively to the normal gut and compared endothelial-specific with ubiquitous Dll4 knockout mice on an Apc (Min/+) background...
January 13, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28050471/spectrum-of-mdct-findings-in-bowel-obstruction-in-a-tertiary-care-rural-hospital-in-northern-india
#7
Ranjana Gupta, Puneet Mittal, Amit Mittal, Sharad Gupta, Kapish Mittal, Arpit Taneja
INTRODUCTION: Multidetector Computed Tomography (MDCT) provides clinically and surgically important information in bowel obstruction. It can depict the severity, level and cause of obstruction. AIM: To depict the spectrum of MDCT findings in cases of small and large bowel obstruction. MATERIALS AND METHODS: Contrast enhanced MDCT examination of 50 patients were retrospectively included in the study who had evidence of clinical as well as MDCT evidence of bowel obstruction and in whom surgical/clinical follow-up for final diagnosis was available...
November 2016: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/27974744/notch-regulates-th17-differentiation-and-controls-trafficking-of-il-17-and-metabolic-regulators-within-th17-cells-in-a-context-dependent-manner
#8
Manuel Coutaz, Benjamin P Hurrell, Floriane Auderset, Haiping Wang, Stefanie Siegert, Gerard Eberl, Ping-Chih Ho, Freddy Radtke, Fabienne Tacchini-Cottier
Th17 cells play critical roles in host defense and autoimmunity. Emerging data support a role for Notch signaling in Th17 cell differentiation but whether it is a positive or negative regulator remains unclear. We report here that T cell-specific deletion of Notch receptors enhances Th17 cell differentiation in the gut, with a corresponding increase in IL-17 secretion. An increase in Th17 cell frequency was similarly observed following immunization of T cell specific Notch mutant mice with OVA/CFA. However, in this setting, Th17 cytokine secretion was impaired, and increased intracellular retention of IL-17 was observed...
December 15, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27634526/virulence-factors-enhance-citrobacter-rodentium-expansion-through-aerobic-respiration
#9
Christopher A Lopez, Brittany M Miller, Fabian Rivera-Chávez, Eric M Velazquez, Mariana X Byndloss, Alfredo Chávez-Arroyo, Kristen L Lokken, Renée M Tsolis, Sebastian E Winter, Andreas J Bäumler
Citrobacter rodentium uses a type III secretion system (T3SS) to induce colonic crypt hyperplasia in mice, thereby gaining an edge during its competition with the gut microbiota through an unknown mechanism. Here, we show that by triggering colonic crypt hyperplasia, the C. rodentium T3SS induced an excessive expansion of undifferentiated Ki67-positive epithelial cells, which increased oxygenation of the mucosal surface and drove an aerobic C. rodentium expansion in the colon. Treatment of mice with the γ-secretase inhibitor dibenzazepine to diminish Notch-driven colonic crypt hyperplasia curtailed the fitness advantage conferred by aerobic respiration during C...
September 16, 2016: Science
https://www.readbyqxmd.com/read/27610020/current-understanding-concerning-intestinal-stem-cells
#10
REVIEW
Shuang Cui, Peng-Yu Chang
In mammals, the intestinal epithelium is a tissue that contains two distinct pools of stem cells: active intestinal stem cells and reserve intestinal stem cells. The former are located in the crypt basement membrane and are responsible for maintaining epithelial homeostasis under intact conditions, whereas the latter exhibit the capacity to facilitate epithelial regeneration after injury. These two pools of cells can convert into each other, maintaining their quantitative balance. In terms of the active intestinal stem cells, their development into functional epithelium is precisely controlled by the following signaling pathways: Wnt/β-catenin, Ras/Raf/Mek/Erk/MAPK, Notch and BMP/Smad...
August 21, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27573849/reg4-deep-crypt-secretory-cells-function-as-epithelial-niche-for-lgr5-stem-cells-in-colon
#11
Nobuo Sasaki, Norman Sachs, Kay Wiebrands, Saskia I J Ellenbroek, Arianna Fumagalli, Anna Lyubimova, Harry Begthel, Maaike van den Born, Johan H van Es, Wouter R Karthaus, Vivian S W Li, Carmen López-Iglesias, Peter J Peters, Jacco van Rheenen, Alexander van Oudenaarden, Hans Clevers
Leucine-rich repeat-containing G-protein coupled receptor 5-positive (Lgr5(+)) stem cells reside at crypt bottoms of the small and large intestine. Small intestinal Paneth cells supply Wnt3, EGF, and Notch signals to neighboring Lgr5(+) stem cells. Whereas the colon lacks Paneth cells, deep crypt secretory (DCS) cells are intermingled with Lgr5(+) stem cells at crypt bottoms. Here, we report regenerating islet-derived family member 4 (Reg4) as a marker of DCS cells. To investigate a niche function, we eliminated DCS cells by using the diphtheria-toxin receptor gene knocked into the murine Reg4 locus...
September 13, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27573785/recapitulating-human-gastric-cancer-pathogenesis-experimental-models-of-gastric-cancer
#12
REVIEW
Lin Ding, Mohamad El Zaatari, Juanita L Merchant
This review focuses on the various experimental models to study gastric cancer pathogenesis, with the role of genetically engineered mouse models (GEMMs) used as the major examples. We review differences in human stomach anatomy compared to the stomachs of the experimental models, including the mouse and invertebrate models such as Drosophila and C. elegans. The contribution of major signaling pathways, e.g., Notch, Hedgehog, AKT/PI3K is discussed in the context of their potential contribution to foregut tumorigenesis...
2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27534699/stem-cell-competition-in-the-gut-insights-from-multi-scale-computational-modelling
#13
Torsten Thalheim, Peter Buske, Jens Przybilla, Karen Rother, Markus Loeffler, Joerg Galle
Three-dimensional (3D) computational tissue models can provide a comprehensive description of tissue dynamics at the molecular, cellular and tissue level. Moreover, they can support the development of hypotheses about cellular interactions and about synergies between major signalling pathways. We exemplify these capabilities by simulation of a 3D single-cell-based model of mouse small intestinal crypts. We analyse the impact of lineage specification, distribution and cellular lifespan on clonal competition and study effects of Notch- and Wnt activation on fixation of mutations within the tissue...
August 2016: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/27534694/necrotizing-enterocolitis-new-insights-into-pathogenesis-and-mechanisms
#14
REVIEW
Diego F Niño, Chhinder P Sodhi, David J Hackam
Necrotizing enterocolitis (NEC) is the most frequent and lethal disease of the gastrointestinal tract of preterm infants. At present, NEC is thought to develop in the premature host in the setting of bacterial colonization, often after administration of non-breast milk feeds, and disease onset is thought to be due in part to a baseline increased reactivity of the premature intestinal mucosa to microbial ligands as compared with the full-term intestinal mucosa. The increased reactivity leads to mucosal destruction and impaired mesenteric perfusion and partly reflects an increased expression of the bacterial receptor Toll-like receptor 4 (TLR4) in the premature gut, as well as other factors that predispose the intestine to a hyper-reactive state in response to colonizing microorganisms...
October 2016: Nature Reviews. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/27184849/programming-of-intestinal-epithelial-differentiation-by-il-33-derived-from-pericryptal-fibroblasts-in-response-to-systemic-infection
#15
Mousumi Mahapatro, Sebastian Foersch, Manuela Hefele, Gui-Wei He, Elisa Giner-Ventura, Tamar Mchedlidze, Markus Kindermann, Stefania Vetrano, Silvio Danese, Claudia Günther, Markus F Neurath, Stefan Wirtz, Christoph Becker
The intestinal epithelium constitutes an efficient barrier against the microbial flora. Here, we demonstrate an unexpected function of IL-33 as a regulator of epithelial barrier functions. Mice lacking IL-33 showed decreased Paneth cell numbers and lethal systemic infection in response to Salmonella typhimurium. IL-33 was produced upon microbial challenge by a distinct population of pericryptal fibroblasts neighboring the intestinal stem cell niche. IL-33 programmed the differentiation of epithelial progenitors toward secretory IEC including Paneth and goblet cells...
May 24, 2016: Cell Reports
https://www.readbyqxmd.com/read/27184041/stem-cells-in-the-intestine-possible-roles-in-pathogenesis-of-irritable-bowel-syndrome
#16
REVIEW
Sutheera Ratanasirintrawoot, Nipan Israsena
Irritable bowel syndrome is one of the most common functional gastrointestinal (GI) disorders that significantly impair quality of life in patients. Current available treatments are still not effective and the pathophysiology of this condition remains unclearly defined. Recently, research on intestinal stem cells has greatly advanced our understanding of various GI disorders. Alterations in conserved stem cell regulatory pathways such as Notch, Wnt, and bone morphogenic protein/TGF- β have been well documented in diseases such as inflammatory bowel diseases and cancer...
July 30, 2016: Journal of Neurogastroenterology and Motility
https://www.readbyqxmd.com/read/27183608/tgf-%C3%AE-signaling-in-dendritic-cells-governs-colonic-homeostasis-by-controlling-epithelial-differentiation-and-the-luminal-microbiota
#17
Sozaburo Ihara, Yoshihiro Hirata, Takako Serizawa, Nobumi Suzuki, Kosuke Sakitani, Hiroto Kinoshita, Yoku Hayakawa, Hayato Nakagawa, Hideaki Ijichi, Keisuke Tateishi, Kazuhiko Koike
Dendritic cells (DCs) mediate host immune responses to gut microbes and play critical roles in inflammatory bowel disease. In this study, we examined the role of TGF-β signaling in DCs in colonic homeostasis. CD11c-cre Tgfbr2(fl/fl) mice developed spontaneous colitis, and CD11c-cre Tgfbr2(fl/+) mice exhibited susceptibility to dextran sulfate sodium-induced colitis. Colitis in these mice was characterized by goblet cell depletion and dysbiosis caused by Enterobacteriaceae enrichment. Wild-type mice gavaged with Enterobacteriaceae from CD11c-cre Tgfbr2(fl/fl) mice feces showed severe colitis after dextran sulfate sodium treatment, whereas those treated with Notch inhibitor exhibited attenuated colonic injury with increased goblet cell numbers, thickened mucus layer, and fewer fecal Enterobacteriaceae Wild-type mice transplanted with CD11c-cre Tgfbr2(fl/fl) bone marrow developed colitis showing increased Jagged1 and Jagged2 in DCs, increased Hes1 levels in epithelium, and goblet cell depletion...
June 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27114183/sept7b-is-required-for-the-differentiation-of-pancreatic-endocrine-progenitors
#18
Surjya Narayan Dash, Elina Hakonen, Jarkko Ustinov, Timo Otonkoski, Olov Andersson, Sanna Lehtonen
Protection or restoration of pancreatic β-cell mass as a therapeutic treatment for type 1 diabetes requires understanding of the mechanisms that drive the specification and development of pancreatic endocrine cells. Septins are filamentous small GTPases that function in the regulation of cell division, cytoskeletal organization and membrane remodeling, and are involved in various tissue-specific developmental processes. However, their role in pancreatic endocrine cell differentiation remains unknown. Here we show by functional manipulation techniques in transgenic zebrafish lines that suppression of sept7b, the zebrafish ortholog of human SEPT7, profoundly increases the number of endocrine progenitors but limits their differentiation, leading to reduction in β- and α-cell mass...
April 26, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27059084/low-oxygen-modulates-multiple-signaling-pathways-increasing-self-renewal-while-decreasing-differentiation-senescence-and-apoptosis-in-stromal-miami-cells
#19
Carmen Rios, Gianluca D'Ippolito, Kevin M Curtis, Gaëtan J-R Delcroix, Lourdes A Gomez, Jimmy El Hokayem, Megan Rieger, Ricardo Parrondo, Alicia de Las Pozas, Carlos Perez-Stable, Guy A Howard, Paul C Schiller
Human bone marrow multipotent mesenchymal stromal cell (hMSC) number decreases with aging. Subpopulations of hMSCs can differentiate into cells found in bone, vasculature, cartilage, gut, and other tissues and participate in their repair. Maintaining throughout adult life such cell subpopulations should help prevent or delay the onset of age-related degenerative conditions. Low oxygen tension, the physiological environment in progenitor cell-rich regions of the bone marrow microarchitecture, stimulates the self-renewal of marrow-isolated adult multilineage inducible (MIAMI) cells and expression of Sox2, Nanog, Oct4a nuclear accumulation, Notch intracellular domain, notch target genes, neuronal transcriptional repressor element 1 (RE1)-silencing transcription factor (REST), and hypoxia-inducible factor-1 alpha (HIF-1α), and additionally, by decreasing the expression of (i) the proapoptotic proteins, apoptosis-inducing factor (AIF) and Bak, and (ii) senescence-associated p53 expression and β-galactosidase activity...
June 1, 2016: Stem Cells and Development
https://www.readbyqxmd.com/read/26921690/stage-specific-regulation-of-the-wnt-%C3%AE-catenin-pathway-enhances-differentiation-of-hescs-into-hepatocytes
#20
Thomas Touboul, Shujuan Chen, Cuong C To, Sergio Mora-Castilla, Karen Sabatini, Robert H Tukey, Louise C Laurent
BACKGROUND & AIMS: Hepatocytes differentiated from human embryonic stem cells (hESCs) have the potential to overcome the shortage of primary hepatocytes for clinical use and drug development. Many strategies for this process have been reported, but the functionality of the resulting cells is incomplete. We hypothesize that the functionality of hPSC-derived hepatocytes might be improved by making the differentiation method more similar to normal in vivo hepatic development. METHODS: We tested combinations of growth factors and small molecules targeting candidate signaling pathways culled from the literature to identify optimal conditions for differentiation of hESCs to hepatocytes, using qRT-PCR for stage-specific markers to identify the best conditions...
June 2016: Journal of Hepatology
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