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https://www.readbyqxmd.com/read/29027285/subtle-deregulation-of-the-wnt-signaling-pathway-through-loss-of-apc2-reduces-the-fitness-of-intestinal-stem-cells
#1
Madeleine A Young, Carl S Daly, Elaine Taylor, Rhiannon James, Alan Richard Clarke, Karen Ruth Reed
The importance of the Wnt-signaling pathway on the regulation and maintenance of the intestinal stem cell (ISC) population is well recognized. However, our current knowledge base is founded on models using systems of gross deregulation of the Wnt-signaling pathway. Given the importance of this signaling pathway on intestinal homeostasis, there is a need to explore the role of more subtle alterations in Wnt-signaling levels within this tissue. Herein, we have used a model of Apc2 loss to meet this aim. Apc2 is a homolog of Apc which can also form a destruction complex capable of binding β-catenin, albeit less efficiently than Apc...
October 12, 2017: Stem Cells
https://www.readbyqxmd.com/read/28992396/alcohol-feeding-in-mice-promotes-colonic-hyperpermeability-and-changes-in-colonic-organoid-stem-cell-fate
#2
Christopher B Forsyth, Maliha Shaikh, Faraz Bishehsari, Garth Swanson, Robin M Voigt, Hemraj Dodiya, Peter Wilkinson, Beata Samelco, Shiwen Song, Ali Keshavarzian
BACKGROUND: Alcohol increases intestinal permeability to pro-inflammatory microbial products that promote liver disease, even after a period of sobriety. We sought to test the hypothesis that alcohol affects intestinal stem cells using an in vivo model and ex vivo organoids generated from jejunum and colon from mice fed chronic alcohol. METHODS: Mice were fed a control or an alcohol diet. Intestinal permeability, liver steatosis/inflammation, and stool short chain fatty acids (SCFA) were measured...
October 9, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28985520/gut-with-the-program-direct-reprogramming-toward-intestinal-epithelium-realized
#3
Angela Nakauka-Ddamba, Christopher J Lengner
Intestinal organoids offer great promise for modeling intestinal diseases; however, harvesting intestinal tissue is invasive and directed hPSC differentiation protocols are laborious and costly. In this issue of Cell Stem Cell, Miura and Suzuki (2017) describe the direct conversion of somatic cells from both mice and humans into robust intestinal epithelial tissue.
October 5, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28982714/interkinetic-nuclear-migration-and-basal-tethering-facilitates-post-mitotic-daughter-separation-in-intestinal-organoids
#4
Thomas D Carroll, Alistair J Langlands, James M Osborne, Ian P Newton, Paul L Appleton, Inke Näthke
Homeostasis of renewing tissues requires balanced proliferation, differentiation and movement. This is particullary important in the intestinal epithelium where lineage tracing suggests that stochastic differentiation choices are intricately coupled to position relative to a niche. To determine how position is achieved we followed proliferating cells in intestinal organoids and discovered that behaviour of mitotic sisters predicted long-term positioning. We found that normally, 70% of sisters remain neighbours while 30% lose contact and separate after cytokinesis...
October 5, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28981121/synthesis-and-characterization-of-well-defined-hydrogel-matrices-and-their-application-to-intestinal-stem-cell-and-organoid-culture
#5
Nikolce Gjorevski, Matthias P Lutolf
Growing cells within an extracellular matrix-like 3D gel is required for, or can improve, the growth of many cell types ex vivo. Here, we describe a protocol for the generation of well-defined matrices for the culture of intestinal stem cells (ISCs) and intestinal organoids. These matrices comprise a poly(ethylene glycol) (PEG) hydrogel backbone functionalized with minimal adhesion cues including RGD (Arg-Gly-Asp), which is sufficient for ISC expansion, and laminin-111, which is required for organoid formation...
November 2017: Nature Protocols
https://www.readbyqxmd.com/read/28978412/layilin-is-critical-for-mediating-hyaluronan-35kda-induced-intestinal-epithelial-tight-junction-protein-zo-1-in-vitro-and-in-vivo
#6
Yeojung Kim, Gail A West, Greeshma Ray, Sean P Kessler, Aaron C Petrey, Claudio Fiocchi, Christine McDonald, Michelle S Longworth, Laura E Nagy, Carol A de la Motte
Tight junction proteins are critical in maintaining homeostatic intestinal permeability. Multiple intestinal inflammatory diseases are correlated with reduced expression of tight junction proteins. We have recently reported that oral treatment of mice with Hyaluronan 35kDa (HA35) increases colonic expression of tight junction protein zonula occludens-1 (ZO-1). Here, we investigate whether HA35 treatment enhances ZO-1 expression by direct interaction with intestinal epithelium in vitro and have identified the HA receptor responsible for HA35-mediated ZO-1 induction in colonic epithelium in vitro and in vivo...
October 1, 2017: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/28974702/human-intestinal-organoids-express-histo-blood-group-antigens-bind-norovirus-vlps-and-support-limited-norovirus-replication
#7
Dongsheng Zhang, Ming Tan, Weiming Zhong, Ming Xia, Pengwei Huang, Xi Jiang
Through pluripotent stem cell (PSC) technology, human intestinal organoids (HIOs) with remarkably similarity to the fetal intestine in cellular composition, architecture, and absorptive/secretory functions have been successfully developed, providing a useful in vitro model system to study the structure and function of human congenital gut and intestinally related diseases. We report here the usefulness of HIOs as a model system to study intestinal carbohydrate expression, virus-host interaction, and replication of human noroviruses (huNoVs)...
October 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28968540/3d-intestinal-organoids-in-metabolic-research-virtual-reality-in-a-dish
#8
REVIEW
Anastasia Tsakmaki, Patricia Fonseca Pedro, Gavin A Bewick
The advent of near physiological organoid technology has produced a step change in our understanding of stem cells and has provided the research community with a powerful new cell based tool to model human physiology and disease. We review the pros and cons of intestinal organoid culture systems. The molecular and genetic tools to manipulate them and how they are being used to answer fundamental questions in metabolic research, including the function of enteroendocrine cells in health and disease.
September 29, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28963394/casein-kinase-1-epsilon-or-1-delta-required-for-wnt-mediated-intestinal-stem-cell-maintenance
#9
Yael Morgenstern, Upasana Das Adhikari, Muneef Ayyash, Ela Elyada, Beáta Tóth, Andreas Moor, Shalev Itzkovitz, Yinon Ben-Neriah
The intestinal epithelium holds an immense regenerative capacity mobilized by intestinal stem cells (ISCs), much of it supported by Wnt pathway activation. Several unique regulatory mechanisms ensuring optimal levels of Wnt signaling have been recognized in ISCs. Here, we identify another Wnt signaling amplifier, CKIε, which is specifically upregulated in ISCs and is essential for ISC maintenance, especially in the absence of its close isoform CKIδ. Co-ablation of CKIδ/ε in the mouse gut epithelium results in rapid ISC elimination, with subsequent growth arrest, crypt-villous shrinking, and rapid mouse death...
September 28, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28960896/powerful-tools-for-genetic-modification-advances-in-gene-editing
#10
REVIEW
Erica A Roesch, Mitchell L Drumm
Recent discoveries and technical advances in genetic engineering, methods called gene or genome editing, provide hope for repairing genes that cause diseases like cystic fibrosis (CF) or otherwise altering a gene for therapeutic benefit. There are both hopes and hurdles with these technologies, with new ideas emerging almost daily. Initial studies using intestinal organoid cultures carrying the common, F508del mutation have shown that gene editing by CRISPR/Cas9 can convert cells lacking CFTR function to cells with normal channel function, providing a precedent that this technology can be harnessed for CF...
September 27, 2017: Pediatric Pulmonology
https://www.readbyqxmd.com/read/28958857/the-function-of-atpase-copper-transporter-atp7b-in-intestine
#11
Hannah Pierson, Abigael Muchenditsi, Byung-Eun Kim, Martina Ralle, Nicholas Zachos, Dominik Huster, Svetlana Lutsenko
BACKGROUND & AIMS: Wilson disease is a disorder of copper (Cu) misbalance caused by mutations in the ATPase copper transporting beta gene (ATP7B). ATP7B is highly expressed in the liver-the major site of Cu accumulation in patients with Wilson disease. The intestine also expresses ATP7B, but little is known about the contribution of intestinal ATP7B to normal intestinal homeostasis or to Wilson disease manifestations. We characterized the role of ATP7B in mouse intestinal organoids and tissues...
September 25, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28949254/a-novel-biosensor-based-on-intestinal-3d-organoids-for-detecting-the-function-of-bcrp
#12
Lei Zhang, Junfang Zhao, Chenmeizi Liang, Mingyao Liu, Feng Xu, Xin Wang
Breast cancer resistance protein (BCRP), a key drug efflux transporter, significantly affects the therapeutic efficacy of many drugs. Thus, screening specific BCRP inhibitors and distinguishing between substrates and non-substrates of BCRP are valuable in drug discovery and development. This study presents a novel BCRP biosensor based on intestinal 3D organoids for rapid and sensitive detection of BCRP function. First, the crypts were isolated from mouse small intestine, and cultured in advanced DMEM/F12 medium to develop intestinal 3D organoids...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28943029/generation-of-mouse-and-human-organoid-forming-intestinal-progenitor-cells-by-direct-lineage-reprogramming
#13
Shizuka Miura, Atsushi Suzuki
Intestinal organoids hold great promise as a valuable tool for studying and treating intestinal diseases. The currently available sources of human intestinal organoids, tissue fragments or pluripotent stem cells, involve invasive procedures or complex differentiation protocols, respectively. Here, we show that a set of four transcription factors, Hnf4α, Foxa3, Gata6, and Cdx2, can directly reprogram mouse fibroblasts to acquire the identity of fetal intestine-derived progenitor cells (FIPCs). These induced FIPCs (iFIPCs) form spherical organoids that develop into adult-type budding organoids containing cells with intestinal stem cell properties...
October 5, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28928734/c3a-enhances-the-formation-of-intestinal-organoids-through-c3ar1
#14
Naoya Matsumoto, Abhigyan Satyam, Mayya Geha, Peter H Lapchak, Jurandir J Dalle Lucca, Maria G Tsokos, George C Tsokos
C3a is important in the regulation of the immune response as well as in the development of organ inflammation and injury. Furthermore, C3a contributes to liver regeneration but its role in intestinal stem cell function has not been studied. We hypothesized that C3a is important for intestinal repair and regeneration. Intestinal organoid formation, a measure of stem cell capacity, was significantly limited in C3-deficient and C3a receptor (C3aR) 1-deficient mice while C3a promoted the growth of organoids from normal mice by supporting Wnt-signaling but not from C3aR1-deficient mice...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28926118/chop-induced-loss-of-intestinal-epithelial-stemness-contributes-to-bile-duct-ligation-induced-cholestatic-liver-injury
#15
Runping Liu, Xiaojiaoyang Li, Zhiming Huang, Derrick Zhao, Bhagyalaxmi Sukka Ganesh, Guanhua Lai, William M Pandak, Phillip B Hylemon, Jasmohan S Bajaj, Arun J Sanyal, Huiping Zhou
Impaired intestinal barrier function promotes the progression of various liver diseases including cholestatic liver disease. The close association of primary sclerosing cholangitis (PSC) with inflammatory bowel disease highlights the importance of the gut-liver axis. It has been reported that bile duct ligation (BDL)-induced liver fibrosis is significantly reduced in C/EBP homologous protein knock out (CHOP(-/-) ) mice. However, the underlying mechanisms remain unclear. In the current study, we demonstrate that BDL induces striking and acute hepatic ER stress responses after 1 day, which return to normal after 3 days...
September 19, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28922991/tissue-engineering-laboratory-models-of-the-small-intestine
#16
Rasha Hatem Dosh, Nicola Jordan-Mahy, Christopher Sammon, Christine Le Maitre
In recent years, three-dimensional (3D) cell culture models of the small intestine have gained much attention. These models support cell proliferation, migration, and differentiation, and encourage tissue organization which is not possible in two-dimensional (2D) culture systems. Furthermore, the use of a wide variety of cell culture scaffolds and support substrates have revealed considerable differences in cell behavior and tissue organization. These systems have been used in combination with intestinal stem cells, organoid units or human colonic adenocarcinoma cell lines such as Caco-2 and HT29-MTX to generate a number of in vitro and in vivo models of the intestine...
September 19, 2017: Tissue Engineering. Part B, Reviews
https://www.readbyqxmd.com/read/28899900/ret-receptor-tyrosine-kinase-sustains-proliferation-and-tissue-maturation-in-intestinal-epithelia
#17
Daniel Perea, Jordi Guiu, Bruno Hudry, Chrysoula Konstantinidou, Alexandra Milona, Dafni Hadjieconomou, Thomas Carroll, Nina Hoyer, Dipa Natarajan, Jukka Kallijärvi, James A Walker, Peter Soba, Nikhil Thapar, Alan J Burns, Kim B Jensen, Irene Miguel-Aliaga
Expression of the Ret receptor tyrosine kinase is a defining feature of enteric neurons. Its importance is underscored by the effects of its mutation in Hirschsprung disease, leading to absence of gut innervation and severe gastrointestinal symptoms. We report a new and physiologically significant site of Ret expression in the intestine: the intestinal epithelium. Experiments in Drosophila indicate that Ret is expressed both by enteric neurons and adult intestinal epithelial progenitors, which require Ret to sustain their proliferation...
September 12, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28898760/live-cell-imaging-of-mouse-intestinal-organoids-reveals-heterogeneity-in-their-oxygenation
#18
Irina A Okkelman, Tara Foley, Dmitri B Papkovsky, Ruslan I Dmitriev
Intestinal organoids are widely applied in stem cell research, regenerative medicine, toxicology, pharmacology, and host-microbe interactions research. The variability of oxidative metabolism for stem and differentiated cell types constituting organoid is known to be important but so far it has not been studied in details. Here, we report the use of live cell microscopy of oxygen via the phosphorescence lifetime imaging microscopy (PLIM) method to address the oxygenation and variability of aerobic metabolism of individual organoids in the culture...
November 2017: Biomaterials
https://www.readbyqxmd.com/read/28891224/smv1-an-extremely-stable-thermophilic-virus-platform-for-nanoparticle-trafficking-in-the-mammalian-gi-tract
#19
Kristine B Uldahl, Seth T Walk, Stephen C Olshefsky, Mark J Young, Xu Peng
AIMS: analysis of the stability and safety of Sulfolobus monocaudavirus 1 (SMV1) during passage through the mammalian GI tract. METHODS AND RESULTS: A major challenge of using nano-vectors to target gut microbiome is their survival during passage through the extremely acidic and proteolytic environment of the mammalian GI tract. Here we investigated the thermo-acidophilic archaeal virus SMV1 as a candidate therapeutic nano-vector for the distal mammalian GI tract microbiome...
September 11, 2017: Journal of Applied Microbiology
https://www.readbyqxmd.com/read/28881081/a-genetically-inducible-porcine-model-of-intestinal-cancer
#20
Morten Møbjerg Callesen, Sigrid Salling Árnadóttir, Iben Lyskjaer, Mai-Britt Worm Ørntoft, Søren Høyer, Frederik Dagnaes-Hansen, Ying Liu, Rong Li, Henrik Callesen, Mads Heilskov Rasmussen, Martin Fogtmann Berthelsen, Martin Kristian Thomsen, Pawel Jan Schweiger, Kim Bak Jensen, Søren Laurberg, Torben Falck Ørntoft, Jannik Ejnar Elverløv-Jakobsen, Claus Lindbjerg Andersen
Transgenic porcine cancer models bring novel possibilities for research. Their physical similarities with humans enable the use of surgical procedures and treatment approaches used for patients, which facilitates clinical translation. Here, we aimed to develop an inducible oncopig model of intestinal cancer. Transgenic (TG) minipigs were generated using somatic cell nuclear transfer by hand-made cloning. The pigs encode two TG cassettes: 1) An Flp-recombinase inducible oncogene cassette containing KRAS-G12D, cMYC, SV40LT - which inhibits p53 - and pRB...
September 7, 2017: Molecular Oncology
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