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https://www.readbyqxmd.com/read/28899900/ret-receptor-tyrosine-kinase-sustains-proliferation-and-tissue-maturation-in-intestinal-epithelia
#1
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/28891224/smv1-an-extremely-stable-thermophilic-virus-platform-for-nanoparticle-trafficking-in-the-mammalian-gi-tract
#2
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/28873141/organoids-reveal-clues-to-gut-brain-communication
#3
Tracy Hampton
No abstract text is available yet for this article.
September 5, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/28802143/extrinsic-control-of-wnt-signaling-in-the-intestine
#4
REVIEW
Stefan Koch
The canonical Wnt/β-catenin signaling pathway is a central regulator of development and tissue homeostasis. In the intestine, Wnt signaling is primarily known as the principal organizer of epithelial stem cell identity and proliferation. Within the last decade, numerous scientific breakthroughs have shed light on epithelial self-organization in the gut, and organoids are now routinely used to study stem cell biology and intestinal pathophysiology. The contribution of non-epithelial cells to Wnt signaling in the gut has received less attention...
August 5, 2017: Differentiation; Research in Biological Diversity
https://www.readbyqxmd.com/read/28789943/reciprocal-inflammatory-signaling-between-intestinal-epithelial-cells-and-adipocytes-in-the-absence-of-immune-cells
#5
Yu Takahashi, Shintaro Sato, Yosuke Kurashima, Chen-Yi Lai, Makoto Otsu, Mikio Hayashi, Takayuki Yamaguchi, Hiroshi Kiyono
Visceral fat accumulation as observed in Crohn's disease and obesity is linked to chronic gut inflammation, suggesting that accumulation of gut adipocytes can trigger local inflammatory signaling. However, direct interactions between intestinal epithelial cells (IECs) and adipocytes have not been investigated, in part because IEC physiology is difficult to replicate in culture. In this study, we originally prepared intact, polarized, and cytokine responsive IEC monolayers from primary or induced pluripotent stem cell-derived intestinal organoids by simple and repeatable methods...
August 2, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28716720/met-signaling-mediates-intestinal-crypt-villus-development-regeneration-and-adenoma-formation-and-is-promoted-by-stem-cell-cd44-isoforms
#6
Sander P J Joosten, Jurrit Zeilstra, Harmen van Andel, R Clinton Mijnals, Joost Zaunbrecher, Annet A M Duivenvoorden, Marc van de Wetering, Hans Clevers, Marcel Spaargaren, Steven T Pals
BACKGROUND & AIMS: Resistance of metastatic human colorectal cancer cells to drugs that block epidermal growth factor (EGF) receptor signaling could be caused by aberrant activity of other receptor tyrosine kinases, activating overlapping signaling pathways. One of these receptor tyrosine kinases could be MET, the receptor for hepatocyte growth factor (HGF). We investigated how MET signaling, and its interaction with CD44 (a putative MET coreceptor regulated by Wnt signaling and highly expressed by intestinal stem cells [ISCs] and adenomas) affects intestinal homeostasis, regeneration, and adenoma formation in mini-gut organoids and mice...
July 14, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28659914/cell-polarization-and-epigenetic-status-shape-the-heterogeneous-response-to-type-iii-interferons-in-intestinal-epithelial-cells
#7
Sudeep Bhushal, Markus Wolfsmüller, Tharini A Selvakumar, Lucas Kemper, Dagmar Wirth, Mathias W Hornef, Hansjörg Hauser, Mario Köster
Type I and type III interferons (IFNs) are crucial components of the first-line antiviral host response. While specific receptors for both IFN types exist, intracellular signaling shares the same Jak-STAT pathway. Due to its receptor expression, IFN-λ responsiveness is restricted mainly to epithelial cells. Here, we display IFN-stimulated gene induction at the single cell level to comparatively analyze the activities of both IFN types in intestinal epithelial cells and mini-gut organoids. Initially, we noticed that the response to both types of IFNs at low concentrations is based on a single cell decision-making determining the total cell intrinsic antiviral activity...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28648659/enterochromaffin-cells-are-gut-chemosensors-that-couple-to-sensory-neural-pathways
#8
Nicholas W Bellono, James R Bayrer, Duncan B Leitch, Joel Castro, Chuchu Zhang, Tracey A O'Donnell, Stuart M Brierley, Holly A Ingraham, David Julius
Dietary, microbial, and inflammatory factors modulate the gut-brain axis and influence physiological processes ranging from metabolism to cognition. The gut epithelium is a principal site for detecting such agents, but precisely how it communicates with neural elements is poorly understood. Serotonergic enterochromaffin (EC) cells are proposed to fulfill this role by acting as chemosensors, but understanding how these rare and unique cell types transduce chemosensory information to the nervous system has been hampered by their paucity and inaccessibility to single-cell measurements...
June 29, 2017: Cell
https://www.readbyqxmd.com/read/28648364/differentiation-of-human-pluripotent-stem-cells-into-colonic-organoids-via-transient-activation-of-bmp-signaling
#9
Jorge O Múnera, Nambirajan Sundaram, Scott A Rankin, David Hill, Carey Watson, Maxime Mahe, Jefferson E Vallance, Noah F Shroyer, Katie L Sinagoga, Adrian Zarzoso-Lacoste, Jonathan R Hudson, Jonathan C Howell, Praneet Chatuvedi, Jason R Spence, John M Shannon, Aaron M Zorn, Michael A Helmrath, James M Wells
Gastric and small intestinal organoids differentiated from human pluripotent stem cells (hPSCs) have revolutionized the study of gastrointestinal development and disease. Distal gut tissues such as cecum and colon, however, have proved considerably more challenging to derive in vitro. Here we report the differentiation of human colonic organoids (HCOs) from hPSCs. We found that BMP signaling is required to establish a posterior SATB2+ domain in developing and postnatal intestinal epithelium. Brief activation of BMP signaling is sufficient to activate a posterior HOX code and direct hPSC-derived gut tube cultures into HCOs...
July 6, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28634937/establishment-of-3d-intestinal-organoid-cultures-from-intestinal-stem-cells
#10
Shinya Sugimoto, Toshiro Sato
The intestinal epithelium is the most rapidly renewed tissue in adult mammals, and its renewal is strictly controlled by intestinal stem cells. Extensive studies using genetic models of intestinal epithelium have revealed the mechanisms underlying the self-renewal of intestinal stem cells. Exploiting this knowledge, we developed a novel 3D culture system that enables the outgrowth of intestinal Lgr5(+) stem cells derived from mouse and human tissues into ever-expanding crypt-villus mini-guts, known as intestinal epithelial organoids...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28615312/stem-cells-in-repair-of-gastrointestinal-epithelia
#11
REVIEW
Amanda Andersson-Rolf, Matthias Zilbauer, Bon-Kyoung Koo, Hans Clevers
Among the endodermal tissues of adult mammals, the gastrointestinal (GI) epithelium exhibits the highest turnover rate. As the ingested food moves along the GI tract, gastric acid, digestive enzymes, and gut resident microbes aid digestion as well as nutrient and mineral absorption. Due to the harsh luminal environment, replenishment of new epithelial cells is essential to maintain organ structure and function during routine turnover and injury repair. Tissue-specific adult stem cells in the GI tract serve as a continuous source for this immense regenerative activity...
July 2017: Physiology
https://www.readbyqxmd.com/read/28550196/il-6-signaling-regulates-small-intestinal-crypt-homeostasis
#12
Victoria Jeffery, Andrew J Goldson, Jack R Dainty, Marcello Chieppa, Anastasia Sobolewski
Gut homeostasis is a tightly regulated process requiring finely tuned complex interactions between different cell types, growth factors, or cytokines and their receptors. Previous work has implicated a role for IL-6 and mucosal immune cells in intestinal regeneration following injury and in promoting inflammation and cancer. We hypothesized that IL-6 signaling could also modulate crypt homeostasis. Using mouse in vitro crypt organoid and in vivo models, this study first demonstrated that exogenous IL-6 promoted crypt organoid proliferation and increased stem cell numbers through pSTAT3 activation in Paneth cells...
May 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28507600/insights-into-the-role-of-the-intestinal-microbiota-in-colon-cancer
#13
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
#14
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
#15
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-support-iscs
#16
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.
July 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
#17
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
#18
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
#19
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...
June 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28336548/nutrient-sensing-by-absorptive-and-secretory-progenies-of-small-intestinal-stem-cells
#20
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
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