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https://www.readbyqxmd.com/read/27634526/virulence-factors-enhance-citrobacter-rodentium-expansion-through-aerobic-respiration
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/26659188/polarized-endosome-dynamics-by-spindle-asymmetry-during-asymmetric-cell-division
#13
Emmanuel Derivery, Carole Seum, Alicia Daeden, Sylvain Loubéry, Laurent Holtzer, Frank Jülicher, Marcos Gonzalez-Gaitan
During asymmetric division, fate determinants at the cell cortex segregate unequally into the two daughter cells. It has recently been shown that Sara (Smad anchor for receptor activation) signalling endosomes in the cytoplasm also segregate asymmetrically during asymmetric division. Biased dispatch of Sara endosomes mediates asymmetric Notch/Delta signalling during the asymmetric division of sensory organ precursors in Drosophila. In flies, this has been generalized to stem cells in the gut and the central nervous system, and, in zebrafish, to neural precursors of the spinal cord...
December 10, 2015: Nature
https://www.readbyqxmd.com/read/26613046/on-the-origin-of-vertebrate-somites
#14
Takayuki Onai, Toshihiro Aramaki, Hidehiko Inomata, Tamami Hirai, Shigeru Kuratani
INTRODUCTION: Somites, blocks of mesoderm tissue located on either side of the neural tube in the developing vertebrate embryo, are derived from mesenchymal cells in the presomitic mesoderm (PSM) and are a defining characteristic of vertebrates. In vertebrates, the somite segmental boundary is determined by Notch signalling and the antagonistic relationship of the downstream targets of Notch, Lfng, and Delta1 in the anterior PSM. The presence of somites in the basal chordate amphioxus (Branchiostoma floridae) indicates that the last common ancestor of chordates also had somites...
2015: Zoological Letters
https://www.readbyqxmd.com/read/26529256/dll4-promotes-continuous-adult-intestinal-lacteal-regeneration-and-dietary-fat-transport
#15
Jeremiah Bernier-Latmani, Christophe Cisarovsky, Cansaran Saygili Demir, Marine Bruand, Muriel Jaquet, Suzel Davanture, Simone Ragusa, Stefanie Siegert, Olivier Dormond, Rui Benedito, Freddy Radtke, Sanjiv A Luther, Tatiana V Petrova
The small intestine is a dynamic and complex organ that is characterized by constant epithelium turnover and crosstalk among various cell types and the microbiota. Lymphatic capillaries of the small intestine, called lacteals, play key roles in dietary fat absorption and the gut immune response; however, little is known about the molecular regulation of lacteal function. Here, we performed a high-resolution analysis of the small intestinal stroma and determined that lacteals reside in a permanent regenerative, proliferative state that is distinct from embryonic lymphangiogenesis or quiescent lymphatic vessels observed in other tissues...
November 3, 2015: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/26528548/mathematical-modelling-of-molecular-pathways-enabling-tumour-cell-invasion-and-migration
#16
David P A Cohen, Loredana Martignetti, Sylvie Robine, Emmanuel Barillot, Andrei Zinovyev, Laurence Calzone
Understanding the etiology of metastasis is very important in clinical perspective, since it is estimated that metastasis accounts for 90% of cancer patient mortality. Metastasis results from a sequence of multiple steps including invasion and migration. The early stages of metastasis are tightly controlled in normal cells and can be drastically affected by malignant mutations; therefore, they might constitute the principal determinants of the overall metastatic rate even if the later stages take long to occur...
November 2015: PLoS Computational Biology
https://www.readbyqxmd.com/read/26436704/mini-gut-organoids-reconstitution-of-the-stem-cell-niche
#17
REVIEW
Shoichi Date, Toshiro Sato
In the adult mammalian body, self-renewal of tissue stem cells is regulated by extracellular niche environments in response to the demands of tissue organization. Intestinal stem cells expressing Lgr5 constantly self-renew in their specific niche at the crypt bottom to maintain rapid turnover of the epithelium. Niche-regulated stem cell self-renewal is perturbed in several mouse genetic models and during human tumorigenesis, suggesting roles for EGF, Wnt, BMP/TGF-β, and Notch signaling. In vitro niche reconstitution capitalizing on this knowledge has enabled the growth of single intestinal stem cells into mini-gut epithelial organoids comprising Lgr5(+) stem cells and all types of differentiated lineages...
2015: Annual Review of Cell and Developmental Biology
https://www.readbyqxmd.com/read/26395488/abcc5-is-required-for-camp-mediated-hindgut-invagination-in-sea-urchin-embryos
#18
Lauren E Shipp, Rose Z Hill, Gary W Moy, Tufan Gökırmak, Amro Hamdoun
ATP-binding cassette (ABC) transporters are evolutionarily conserved proteins that pump diverse substrates across membranes. Many are known to efflux signaling molecules and are extensively expressed during development. However, the role of transporters in moving extracellular signals that regulate embryogenesis is largely unexplored. Here, we show that a mesodermal ABCC (MRP) transporter is necessary for endodermal gut morphogenesis in sea urchin embryos. This transporter, Sp-ABCC5a (C5a), is expressed in pigment cells and their precursors, which are a subset of the non-skeletogenic mesoderm (NSM) cells...
October 15, 2015: Development
https://www.readbyqxmd.com/read/26288152/the-interplay-between-wnt-mediated-expansion-and-negative-regulation-of-growth-promotes-robust-intestinal-crypt-structure-and-homeostasis
#19
Huijing Du, Qing Nie, William R Holmes
The epithelium of the small intestinal crypt, which has a vital role in protecting the underlying tissue from the harsh intestinal environment, is completely renewed every 4-5 days by a small pool of stem cells at the base of each crypt. How is this renewal controlled and homeostasis maintained, particularly given the rapid nature of this process? Here, based on the recent observations from in vitro "mini gut" studies, we use a hybrid stochastic model of the crypt to investigate how exogenous niche signaling (from Wnt and BMP) combines with auto-regulation to promote homeostasis...
August 2015: PLoS Computational Biology
https://www.readbyqxmd.com/read/26286942/the-thyroid-hormone-nuclear-receptor-tr%C3%AE-1-controls-the-notch-signaling-pathway-and-cell-fate-in-murine-intestine
#20
Maria Sirakov, Amina Boussouar, Elsa Kress, Carla Frau, Imtiaz Nisar Lone, Julien Nadjar, Dimitar Angelov, Michelina Plateroti
Thyroid hormones control various aspects of gut development and homeostasis. The best-known example is in gastrointestinal tract remodeling during amphibian metamorphosis. It is well documented that these hormones act via the TR nuclear receptors, which are hormone-modulated transcription factors. Several studies have shown that thyroid hormones regulate the expression of several genes in the Notch signaling pathway, indicating a possible means by which they participate in the control of gut physiology. However, the mechanisms and biological significance of this control have remained unexplored...
August 15, 2015: Development
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