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https://www.readbyqxmd.com/read/28507600/insights-into-the-role-of-the-intestinal-microbiota-in-colon-cancer
#1
REVIEW
Sofia Oke, Alberto Martin
The intestinal microbiota consists of a dynamic organization of bacteria, viruses, archaea, and fungal species essential for maintaining gut homeostasis and protecting the host against pathogenic invasion. When dysregulated, the intestinal microbiota can contribute to colorectal cancer development. Though the microbiota is multifaceted in its ability to induce colorectal cancer, this review will focus on the capability of the microbiota to induce colorectal cancer through the modulation of immune function and the production of microbial-derived metabolites...
May 2017: Therapeutic Advances in Gastroenterology
https://www.readbyqxmd.com/read/28488235/emulating-host-microbiome-ecosystem-of-human-gastrointestinal-tract-in-vitro
#2
Gun-Seok Park, Min Hee Park, Woojung Shin, Connie Zhao, Sameer Sheikh, So Jung Oh, Hyun Jung Kim
The human gut microbiome performs prodigious physiological functions such as production of microbial metabolites, modulation of nutrient digestion and drug metabolism, control of immune system, and prevention of infection. Paradoxically, gut microbiome can also negatively orchestrate the host responses in diseases or chronic disorders, suggesting that the regulated and balanced host-gut microbiome crosstalk is a salient prerequisite in gastrointestinal physiology. To understand the pathophysiological role of host-microbiome crosstalk, it is critical to recreate in vivo relevant models of the host-gut microbiome ecosystem in human...
May 10, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/28484457/type-i-and-type-iii-interferons-display-different-dependency-on-mitogen-activated-protein-kinases-to-mount-an-antiviral-state-in-the-human-gut
#3
Kalliopi Pervolaraki, Megan L Stanifer, Stephanie Münchau, Lynnsey A Renn, Dorothee Albrecht, Stefan Kurzhals, Elena Senís, Dirk Grimm, Jutta Schröder-Braunstein, Ronald L Rabin, Steeve Boulant
Intestinal epithelial cells (IECs) are constantly exposed to commensal flora and pathogen challenges. How IECs regulate their innate immune response to maintain gut homeostasis remains unclear. Interferons (IFNs) are cytokines produced during infections. While type I IFN receptors are ubiquitously expressed, type III IFN receptors are expressed only on epithelial cells. This epithelium specificity strongly suggests exclusive functions at epithelial surfaces, but the relative roles of type I and III IFNs in the establishment of an antiviral innate immune response in human IECs are not clearly defined...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28429766/beyond-growth-signaling-paneth-cells-metabolically-suppport-iscs
#4
Talya L Dayton, Hans Clevers
Single Lgr5 intestinal stem cells (ISCs) can be expanded in vitro into epithelial organoids or "mini-guts", self-organizing cellular structures that recreate the intestinal differentiation program; Paneth cells, which constitute the intestinal stem cell niche, secrete stem cell growth signals, and are thus essential for this process. In a recent paper published in Nature, Rodríguez-Colman et al. describe how Paneth cells may be supporting the metabolic state of ISCs.
April 21, 2017: Cell Research
https://www.readbyqxmd.com/read/28424327/rig-i-mavs-and-sting-signaling-promote-gut-integrity-during-irradiation-and-immune-mediated-tissue-injury
#5
Julius C Fischer, Michael Bscheider, Gabriel Eisenkolb, Chia-Ching Lin, Alexander Wintges, Vera Otten, Caroline A Lindemans, Simon Heidegger, Martina Rudelius, Sébastien Monette, Kori A Porosnicu Rodriguez, Marco Calafiore, Sophie Liebermann, Chen Liu, Stefan Lienenklaus, Siegfried Weiss, Ulrich Kalinke, Jürgen Ruland, Christian Peschel, Yusuke Shono, Melissa Docampo, Enrico Velardi, Robert R Jenq, Alan M Hanash, Jarrod A Dudakov, Tobias Haas, Marcel R M van den Brink, Hendrik Poeck
The molecular pathways that regulate the tissue repair function of type I interferon (IFN-I) during acute tissue damage are poorly understood. We describe a protective role for IFN-I and the RIG-I/MAVS signaling pathway during acute tissue damage in mice. Mice lacking mitochondrial antiviral-signaling protein (MAVS) were more sensitive to total body irradiation- and chemotherapy-induced intestinal barrier damage. These mice developed worse graft-versus-host disease (GVHD) in a preclinical model of allogeneic hematopoietic stem cell transplantation (allo-HSCT) than did wild-type mice...
April 19, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28404872/synthetic-associative-learning-in-engineered-multicellular-consortia
#6
Javier Macia, Blai Vidiella, Ricard V Solé
Associative learning (AL) is one of the key mechanisms displayed by living organisms in order to adapt to their changing environments. It was recognized early as a general trait of complex multicellular organisms but is also found in 'simpler' ones. It has also been explored within synthetic biology using molecular circuits that are directly inspired in neural network models of conditioning. These designs involve complex wiring diagrams to be implemented within one single cell, and the presence of diverse molecular wires become a challenge that might be very difficult to overcome...
April 2017: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/28380450/the-g-protein-coupled-receptor-56-expressed-in-colonic-stem-and-cancer-cells-binds-progastrin-to-promote-proliferation-and-carcinogenesis
#7
Guangchun Jin, Kosuke Sakitani, Hongshan Wang, Ying Jin, Alexander Dubeykovskiy, Daniel L Worthley, Yagnesh Tailor, Timothy C Wang
Overexpression of human progastrin increases colonic mucosal proliferation and colorectal cancer progression in mice. The G-protein coupled receptor 56 (GPR56) is known to regulate cell adhesion, migration, proliferation and stem cell biology, but its expression in the gut has not been studied. We hypothesized that the promotion of colorectal cancer by progastrin may be mediated in part through GPR56. Here, we found that GPR56 expresses in rare colonic crypt cells that lineage trace colonic glands consistent with GPR56 marking long-lived colonic stem-progenitor cells...
March 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28336548/nutrient-sensing-by-absorptive-and-secretory-progenies-of-small-intestinal-stem-cells
#8
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 (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...
March 23, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28292848/intestinal-epithelial-organoids-fuse-to-form-self-organizing-tubes-in-floating-collagen-gels
#9
Norman Sachs, Yoshiyuki Tsukamoto, Pekka Kujala, Peter J Peters, Hans Clevers
Multiple recent examples highlight how stem cells can self-organize in vitro to establish organoids that closely resemble their in vivo counterparts. Single Lgr5(+) mouse intestinal stem cells can be cultured under defined conditions forming ever-expanding epithelial organoids that retain cell polarization, cell type diversity and anatomical organization of the in vivo epithelium. Although exhibiting a remarkable level of self-organization, the so called 'mini-guts' have a closed cystic structure of microscopic size...
March 15, 2017: Development
https://www.readbyqxmd.com/read/28275681/gastrointestinal-organoids-understanding-the-molecular-basis-of-the-host-microbe-interface
#10
REVIEW
David R Hill, Jason R Spence
In recent years, increasing attention has been devoted to the concept that microorganisms play an integral role in human physiology and pathophysiology. Despite this, the molecular basis of host-pathogen and host-symbiont interactions in the human intestine remains poorly understood owing to the limited availability of human tissue, and the biological complexity of host-microbe interactions. Over the past decade, technological advances have enabled long-term culture of organotypic intestinal tissue derived from human subjects and from human pluripotent stem cells, and these in vitro culture systems already have shown the potential to inform our understanding significantly of host-microbe interactions...
March 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28191783/concise-review-the-potential-use-of-intestinal-stem-cells-to-treat-patients-with-intestinal-failure
#11
Sung Noh Hong, James C Y Dunn, Matthias Stelzner, Martín G Martín
Intestinal failure is a rare life-threatening condition that results in the inability to maintain normal growth and hydration status by enteral nutrition alone. Although parenteral nutrition and whole organ allogeneic transplantation have improved the survival of these patients, current therapies are associated with a high risk for morbidity and mortality. Development of methods to propagate adult human intestinal stem cells (ISCs) and pluripotent stem cells raises the possibility of using stem cell-based therapy for patients with monogenic and polygenic forms of intestinal failure...
February 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28159716/cellular-self-assembly-and-biomaterials-based-organoid-models-of-development-and-diseases
#12
REVIEW
Shivem B Shah, Ankur Singh
Organogenesis and morphogenesis have informed our understanding of physiology, pathophysiology, and avenues to create new curative and regenerative therapies. Thus far, this understanding has been hindered by the lack of a physiologically relevant yet accessible model that affords biological control. Recently, three-dimensional ex vivo cellular cultures created through cellular self-assembly under natural extracellular matrix cues or through biomaterial-based directed assembly have been shown to physically resemble and recapture some functionality of target organs...
January 31, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28123937/fermentable-carbohydrate-stimulates-ffar2-dependent-colonic-pyy-cell-expansion%C3%A2-to%C3%A2-increase-satiety
#13
Lucy Brooks, Alexander Viardot, Anastasia Tsakmaki, Emilie Stolarczyk, Jane K Howard, Patrice D Cani, Amandine Everard, Michelle L Sleeth, Arianna Psichas, Jelena Anastasovskaj, Jimmy D Bell, Kim Bell-Anderson, Charles R Mackay, Mohammad A Ghatei, Stephen R Bloom, Gary Frost, Gavin A Bewick
OBJECTIVE: Dietary supplementation with fermentable carbohydrate protects against body weight gain. Fermentation by the resident gut microbiota produces short-chain fatty acids, which act at free fatty acid receptor 2 (FFAR2). Our aim was to test the hypothesis that FFAR2 is important in regulating the beneficial effects of fermentable carbohydrate on body weight and to understand the role of gut hormones PYY and GLP-1. METHODS: Wild-type or Ffar2(-/-) mice were fed an inulin supplemented or control diet...
January 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28097227/a-xenogeneic-free-system-generating-functional-human-gut-organoids-from-pluripotent-stem-cells
#14
Hajime Uchida, Masakazu Machida, Takumi Miura, Tomoyuki Kawasaki, Takuya Okazaki, Kengo Sasaki, Seisuke Sakamoto, Noriaki Ohuchi, Mureo Kasahara, Akihiro Umezawa, Hidenori Akutsu
Functional intestines are composed of cell types from all 3 primary germ layers and are generated through a highly orchestrated and serial developmental process. Directed differentiation of human pluripotent stem cells (hPSCs) has been shown to yield gut-specific cell types; however, these structures do not reproduce critical functional interactions between cell types of different germ layers. Here, we developed a simple protocol for the generation of mature functional intestinal organoids from hPSCs under xenogeneic-free conditions...
January 12, 2017: JCI Insight
https://www.readbyqxmd.com/read/28074039/cd34-mesenchymal-cells-are-a-major-component-of-the-intestinal-stem-cells-niche-at-homeostasis-and-after-injury
#15
Igor Stzepourginski, Giulia Nigro, Jean-Marie Jacob, Sophie Dulauroy, Philippe J Sansonetti, Gérard Eberl, Lucie Peduto
The intestinal epithelium is continuously renewed by intestinal epithelial stem cells (IESCs) positioned at the base of each crypt. Mesenchymal-derived factors are essential to maintain IESCs; however, the cellular composition and development of such mesenchymal niche remains unclear. Here, we identify pericryptal CD34(+) Gp38(+) αSMA(-) mesenchymal cells closely associated with Lgr5(+) IESCs. We demonstrate that CD34(+) Gp38(+) cells are the major intestinal producers of the niche factors Wnt2b, Gremlin1, and R-spondin1, and are sufficient to promote maintenance of Lgr5(+) IESCs in intestinal organoids, an effect mainly mediated by Gremlin1...
January 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27640087/modeling-infectious-diseases-and-host-microbe-interactions-in-gastrointestinal-organoids
#16
REVIEW
Sina Bartfeld
Advances in stem cell research have allowed the development of 3-dimensional (3D) primary cell cultures termed organoid cultures, as they closely mimic the in vivo organization of different cell lineages. Bridging the gap between 2-dimensional (2D) monotypic cancer cell lines and whole organisms, organoids are now widely applied to model development and disease. Organoids hold immense promise for addressing novel questions in host-microbe interactions, infectious diseases and the resulting inflammatory conditions...
December 15, 2016: Developmental Biology
https://www.readbyqxmd.com/read/27638919/concise-review-the-potential-use-of-intestinal-stem-cells-to-treat-patients-with-intestinal-failure
#17
Sung Noh Hong, James C Y Dunn, Matthias Stelzner, Martín G Martín
: Intestinal failure is a rare life-threatening condition that results in the inability to maintain normal growth and hydration status by enteral nutrition alone. Although parenteral nutrition and whole organ allogeneic transplantation have improved the survival of these patients, current therapies are associated with a high risk for morbidity and mortality. Development of methods to propagate adult human intestinal stem cells (ISCs) and pluripotent stem cells raises the possibility of using stem cell-based therapy for patients with monogenic and polygenic forms of intestinal failure...
September 16, 2016: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/27628134/intestinal-organoids-as-a-novel-tool-to-study-microbes-epithelium-interactions
#18
Giulia Nigro, Melissa Hanson, Cindy Fevre, Marc Lecuit, Philippe J Sansonetti
The gut, particularly the colon, is the host of approximately 1000 bacterial species, the so-called gut microbiota. The relationship between the gut microbiota and the host is symbiotic and mutualistic, influencing many aspects of the biology of the host. This homeostatic balance can be disrupted by enteric pathogens, such as Shigella flexneri or Listeria monocytogenes, which are able to invade the epithelial layer and consequently subvert physiological functions. To study the host-microbe interactions in vitro, the crypt culture model, known as intestinal organoids, is a powerful tool...
September 15, 2016: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27573849/reg4-deep-crypt-secretory-cells-function-as-epithelial-niche-for-lgr5-stem-cells-in-colon
#19
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/27521455/gastrointestinal-organoids-how-they-gut-it-out
#20
REVIEW
Sebastian R Merker, Jürgen Weitz, Daniel E Stange
The gastrointestinal tract is characterized by a self-renewing epithelium fueled by adult stem cells residing at the bottom of the intestinal crypt and gastric glands. Their activity and proliferation is strongly dependent on complex signaling pathways involving other crypt/gland cells as well as surrounding stromal cells. In recent years organoids are becoming increasingly popular as a new and powerful tool to study developmental or other biological processes. Organoids retain morphological and molecular patterns of the tissue they are derived from, are self-organizing, relatively simple to handle and accessible to genetic engineering...
December 15, 2016: Developmental Biology
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