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Gut stem cell

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https://www.readbyqxmd.com/read/29141958/dna-methylation-defines-regional-identity-of-human-intestinal-epithelial-organoids-and-undergoes-dynamic-changes-during-development
#1
Judith Kraiczy, Komal M Nayak, Kate J Howell, Alexander Ross, Jessica Forbester, Camilla Salvestrini, Roxana Mustata, Sally Perkins, Amanda Andersson-Rolf, Esther Leenen, Anke Liebert, Ludovic Vallier, Philip C Rosenstiel, Oliver Stegle, Gordon Dougan, Robert Heuschkel, Bon-Kyoung Koo, Matthias Zilbauer
OBJECTIVE: Human intestinal epithelial organoids (IEOs) are increasingly being recognised as a highly promising translational research tool. However, our understanding of their epigenetic molecular characteristics and behaviour in culture remains limited. DESIGN: We performed genome-wide DNA methylation and transcriptomic profiling of human IEOs derived from paediatric/adult and fetal small and large bowel as well as matching purified human gut epithelium. Furthermore, organoids were subjected to in vitro differentiation and genome editing using CRISPR/Cas9 technology...
November 15, 2017: Gut
https://www.readbyqxmd.com/read/29120819/towards-a-defined-ecm-and-small-molecule-based-monolayer-culture-system-for-the-expansion-of-mouse-and-human-intestinal-stem-cells
#2
Zhixiang Tong, Keir Martyn, Andy Yang, Xiaolei Yin, Benjamin E Mead, Nitin Joshi, Nicholas E Sherman, Robert S Langer, Jeffrey M Karp
Current ISC culture systems face significant challenges such as animal-derived or undefined matrix compositions, batch-to-batch variability (e.g. Matrigel-based organoid culture), and complexity of assaying cell aggregates such as organoids which renders the research and clinical translation of ISCs challenging. Here, through screening for suitable ECM components, we report a defined, collagen based monolayer culture system that supports the growth of mouse and human intestinal epithelial cells (IECs) enriched for an Lgr5(+) population comparable or higher to the levels found in a standard Matrigel-based organoid culture...
October 26, 2017: Biomaterials
https://www.readbyqxmd.com/read/29109476/the-major-targets-of-acute-norovirus-infection-are-immune-cells-in-the-gut-associated-lymphoid-tissue
#3
Katrina R Grau, Alexa N Roth, Shu Zhu, Abel Hernandez, Natacha Colliou, Bayli B DiVita, Drake T Philip, Cara Riffe, Benoit Giasson, Shannon M Wallet, Mansour Mohamadzadeh, Stephanie M Karst
Noroviruses are the leading cause of food-borne gastroenteritis outbreaks and childhood diarrhoea globally, estimated to be responsible for 200,000 deaths in children each year (1-4) . Thus, reducing norovirus-associated disease is a critical priority. Development of vaccines and therapeutics has been hindered by the limited understanding of basic norovirus pathogenesis and cell tropism. While macrophages, dendritic cells, B cells and stem-cell-derived enteroids can all support infection of certain noroviruses in vitro (5-7) , efforts to define in vivo norovirus cell tropism have generated conflicting results...
November 6, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/29108021/hippo-tgf-%C3%AE-and-src-mapk-pathways-regulate-transcription-of-the-upd3-cytokine-in-drosophila-enterocytes-upon-bacterial-infection
#4
Philip Houtz, Alessandro Bonfini, Xi Liu, Jonathan Revah, Aurélien Guillou, Mickael Poidevin, Korneel Hens, Hsin-Yi Huang, Bart Deplancke, Yu-Chen Tsai, Nicolas Buchon
Cytokine signaling is responsible for coordinating conserved epithelial regeneration and immune responses in the digestive tract. In the Drosophila midgut, Upd3 is a major cytokine, which is induced in enterocytes (EC) and enteroblasts (EB) upon oral infection, and initiates intestinal stem cell (ISC) dependent tissue repair. To date, the genetic network directing upd3 transcription remains largely uncharacterized. Here, we have identified the key infection-responsive enhancers of the upd3 gene and show that distinct enhancers respond to various stresses...
November 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29097037/better-early-outcome-with-enteral-rather-than-parenteral-nutrition-in-children-undergoing-mac-allo-sct
#5
F Gonzales, B Bruno, M Alarcón Fuentes, E De Berranger, D Guimber, H Behal, V Gandemer, A Spiegel, A Sirvent, I Yakoub-Agha, B Nelken, A Duhamel, D Seguy
There is no consensus on the type of nutritional support to introduce in children undergoing allogeneic stem cell transplantation (allo-SCT) after myeloablative conditioning (MAC). This retrospective, multicenter, observational study compared the early administration of enteral nutrition (EN group, n = 97) versus parenteral nutrition (PN group, n = 97) in such patients with matching for important covariates. The primary endpoint was the study of day 100 overall mortality. The early outcome at day 100 was better in EN group regarding mortality rate (1% vs...
October 12, 2017: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/29081665/clinical-significance-of-fusobacterium-nucleatum-epithelial-mesenchymal-transition-and-cancer-stem-cell-markers-in-stage-iii-iv-colorectal-cancer-patients
#6
Xuebing Yan, Liguo Liu, Hao Li, Huanlong Qin, Zhenliang Sun
Colorectal cancer (CRC) is a common digestive malignancy and emerging studies have closely linked its initiation and development with gut microbiota changes. Fusobacterium nucleatum (Fn) has been recently identified as a pathogenic bacteria for CRC; however, its prognostic significance for patients is poorly investigated and is less for patients within late stage. Therefore, in this study, we made efforts to analyze its level and prognostic significance in a retrospective cohort of 280 stage III/IV CRC patients...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29075267/pd-1-controls-tonic-signaling-and-lymphopenia-induced-proliferation-of-t-lymphocytes
#7
Kristofor K Ellestad, Jiaxin Lin, Louis Boon, Colin C Anderson
Recovery of the T lymphocyte compartment within a lymphopenic host by lymphopenia-induced proliferation (LIP) is regulated by inter- and intraclonal competition for limited resources, including homeostatic cytokines and peptide:MHC (pMHC) complexes with which the TCR can interact at least weakly to yield a tonic signal. Importantly, the process of LIP can synergize with other factors that promote T cell activation to drive inflammatory disease. While reconstitution of the lymphoid compartment of immune deficient Rag(-/-) mice by transfer of wild-type hematopoietic stem cells (HSC) does not generally result in an overt disease phenotype, transfer of HSC deficient in expression of the co-inhibitory molecule PD-1 results in severe systemic autoimmunity driven by newly generated T cells that emerge from the thymus into the periphery and undergo LIP...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29073260/etanercept-for-steroid-refractory-acute-graft-versus-host-disease-a-single-center-experience
#8
Cornelis N De Jong, Lotte Saes, Clara P W Klerk, Marjolein Van der Klift, Jan J Cornelissen, Annoek E C Broers
BACKGROUND: Acute graft-versus-host disease (aGVHD) is an important complication of allogeneic stem cell transplantation (alloSCT). High dose glucocorticosteroids, are currently recommended as first-line treatment for grade II-IV aGVHD resulting in overall complete responses (CR) in 40%-50% of patients. No standard second-line regimen has been established. Different options have been reported, including anti-TNFα antibodies. METHODS: We retrospectively reviewed the outcome of 15 patients with steroid-refractory (SR) aGVHD treated with etanercept at our institution...
2017: PloS One
https://www.readbyqxmd.com/read/29066578/r-spondin1-expands-paneth-cells-and-prevents-dysbiosis-induced-by-graft-versus-host-disease
#9
Eiko Hayase, Daigo Hashimoto, Kiminori Nakamura, Clara Noizat, Reiki Ogasawara, Shuichiro Takahashi, Hiroyuki Ohigashi, Yuki Yokoi, Rina Sugimoto, Satomi Matsuoka, Takahide Ara, Emi Yokoyama, Tomohiro Yamakawa, Ko Ebata, Takeshi Kondo, Rina Hiramine, Tomoyasu Aizawa, Yoshitoshi Ogura, Tetsuya Hayashi, Hiroshi Mori, Ken Kurokawa, Kazuma Tomizuka, Tokiyoshi Ayabe, Takanori Teshima
The intestinal microbial ecosystem is actively regulated by Paneth cell-derived antimicrobial peptides such as α-defensins. Various disorders, including graft-versus-host disease (GVHD), disrupt Paneth cell functions, resulting in unfavorably altered intestinal microbiota (dysbiosis), which further accelerates the underlying diseases. Current strategies to restore the gut ecosystem are bacteriotherapy such as fecal microbiota transplantation and probiotics, and no physiological approach has been developed so far...
October 24, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29049360/the-bacterial-virulence-factor-caga-induces-microbial-dysbiosis-that-contributes-to-excessive-epithelial-cell-proliferation-in-the-drosophila-gut
#10
Tiffani Alvey Jones, Diane Z Hernandez, Zoë C Wong, Anica M Wandler, Karen Guillemin
Gut microbiota facilitate many aspects of human health and development, but dysbiotic microbiota can promote hyperplasia and inflammation and contribute to human diseases such as cancer. Human patients infected with the gastric cancer-causing bacterium Helicobacter pylori have altered microbiota; however, whether dysbiosis contributes to disease in this case is unknown. Many H. pylori human disease phenotypes are associated with a potent virulence protein, CagA, which is translocated into host epithelial cells where it alters cell polarity and manipulates host-signaling pathways to promote disease...
October 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29040501/tissue-damage-induced-midgut-stem-cell-proliferation-and-microbial-dysbiosis-in-spodoptera-litura
#11
Neeti Pandey, Raman Rajagopal
In the past decade, gut microbiota has come to the fore in search for the cause of disregulation in intestinal homeostasis. Here, we report a possible link between gut microbial dynamics and stress-inducing factors using the leaf worm moth Spodoptera litura as a model organism. Investigation reveals that S. litura exhibits dysbiosis i.e. alteration in the gut microbiota composition that might induce or suppress inflammation upon exposure to dextran sulfate sodium salt, a tissue damaging agent (DSS, 40 kD). It primarily corresponds to an expansion of the bacterial phylotypes Enterobacter sp...
November 1, 2017: FEMS Microbiology Ecology
https://www.readbyqxmd.com/read/29031500/transcription-and-signaling-regulators-in-developing-neuronal-subtypes-of-mouse-and-human-enteric-nervous-system
#12
Fatima Memic, Viktoria Knoflach, Khomgrit Morarach, Rebecca Sadler, Catia Laranjeira, Jens Hjerling-Leffler, Erik Sundström, Vassilis Pachnis, Ulrika Marklund
BACKGROUND AND AIMS: The enteric nervous system (ENS) regulates gastrointestinal function via different subtypes of neurons, organized into fine-tuned neural circuits. It is not clear how cell diversity is created within the embryonic ENS-information required for development of cell-based therapies and models of enteric neuropathies. We aimed to identify proteins that regulate ENS differentiation and network formation. METHODS: We generated and compared RNA expression profiles of the entire ENS, ENS progenitor cells, and non-ENS gut cells of mice, collected at embryonic days 11...
October 11, 2017: Gastroenterology
https://www.readbyqxmd.com/read/29030814/determination-of-histone-2b-green-fluorescent-protein-gfp-retention-in-intestinal-stem-cells
#13
Kevin R Hughes, Yashwant R Mahida
The epithelium of the gastrointestinal tract represents the interface between the luminal contents of the gut and that of the host tissues and plays a central role not only in regulating absorption of dietary nutrients but also in providing a barrier to prevent the entry of bacteria and other pathogens. Repair and replacement of damaged aging cells within the epithelium is modulated by stem cells, which are located in the intestinal crypts of the small intestine.Two distinct populations of intestinal stem cells have been described in the literature, one population at the very base of the crypt and a second population of long-lived stem cells located just above the Paneth cell zone...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28992793/the-short-chain-fatty-acid-propionate-inhibits-adipogenic-differentiation-of-human-chorion-derived-mesenchymal-stem-cells-through-the-free-fatty-acid-receptor-2
#14
Judit Iván, Evelin Major, Adrienn Sipos, Katalin Kovács, Dániel Horváth, István Tamás, Péter Bay, Viktor Dombrádi, Beáta Lontay
Free fatty acid receptor 2 (FFAR2, also known as GPR43) is a G-protein-coupled receptor activated by short-chain fatty acids that are produced by gut microbiota through fermentation of nondigestible carbohydrates. FFAR2 functions as a metabolic sensor and is expressed in metabolically active tissues, such as adipose tissue. Earlier studies proved the connection between FFAR2 and adipocyte differentiation in mice. The aim of this study was to investigate the implication of FFAR2 receptor in adipogenesis in human chorion-derived mesenchymal stem cells (cMSCs)...
November 14, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28986650/expression-of-stem-cell-factors-in-the-adult-sea-cucumber-digestive-tube
#15
Vladimir Mashanov, Olga Zueva, Daria Mashanova, José E García-Arrarás
Homeostatic cell turnover has been extensively characterized in mammals. In their adult tissues, lost or aging differentiated cells are replenished by a self-renewing cohort of stem cells. The stem cells have been particularly well studied in the intestine and are clearly identified by the expression of marker genes including Lgr5 and Bmi1. It is, however, unknown if the established principles of tissue renewal learned from mammals would be operating in non-mammalian systems. Here, we study homeostatic cell turnover in the sea cucumber digestive tube, the organ with high tissue plasticity even in adult animals...
October 7, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28985520/gut-with-the-program-direct-reprogramming-toward-intestinal-epithelium-realized
#16
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/28982685/drosophila-atg16-promotes-enteroendocrine-cell-differentiation-via-regulation-of-intestinal-slit-robo-signaling
#17
Péter Nagy, Zsuzsanna Szatmári, Gyöngyvér O Sándor, Mónika Lippai, Krisztina Hegedűs, Gábor Juhász
Genetic variations of Atg16L1, Slit and Rab19 predispose to the development of inflammatory bowel disease (IBD), but the relationship of these mutations is unclear. Here we show that in Drosophila guts lacking the WD40 domain of Atg16, pre-enteroendocrine cells (pre-EEs) accumulate that fail to differentiate into properly functioning secretory EEs. Mechanistically, loss of Atg16 or its binding partner Rab19 impairs Slit production, which normally inhibits EE generation by activating Robo signaling in stem cells...
October 5, 2017: Development
https://www.readbyqxmd.com/read/28974702/human-intestinal-organoids-express-histo-blood-group-antigens-bind-norovirus-vlps-and-support-limited-norovirus-replication
#18
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/28970139/fetal-gut-like-differentiation-in-gallbladder-cancer
#19
Kei Koyama, Daichi Maeda, Daisuke Tamura, Chisato Narita, Yukitsugu Kudo-Asabe, Tsutomu Sato, Yuzo Yamamoto, Masato Sageshima, Hiroshi Nanjo, Akiteru Goto
Adenocarcinomas showing fetal gut-like (enteroblastic) differentiation can arise in a variety of organs, and are frequently accompanied by an elevated serum alpha-fetoprotein (AFP) level. However, no study has investigated fetal gut-like differentiation in gallbladder cancer in detail. Herein, we performed morphological and immunohistochemical analyses of fetal-gut like differentiation in 49 consecutive gallbladder cancer cases. The expression of Sal-like protein 4 (SALL4), an embryonic stem cell marker reported to represent fetal gut-like differentiation, as well as other oncofetal proteins, including glypican-3 (GPC3) and AFP, were assessed...
September 29, 2017: Human Pathology
https://www.readbyqxmd.com/read/28967895/associations-between-acute-gastrointestinal-gvhd-and-the-baseline-gut-microbiota-of-allogeneic-hematopoietic-stem-cell-transplant-recipients-and-donors
#20
C Liu, D N Frank, M Horch, S Chau, D Ir, E A Horch, K Tretina, K van Besien, C A Lozupone, V H Nguyen
Growing evidence suggests that host-microbiota interactions influence GvHD risk following allogeneic hematopoietic stem cell transplant. However, little is known about the influence of the transplant recipient's pre-conditioning microbiota nor the influence of the transplant donor's microbiota. Our study examines associations between acute gastrointestinal GvHD (agGvHD) and 16S rRNA fecal bacterial profiles in a prospective cohort of N=57 recipients before preparative conditioning, as well as N=22 of their paired HLA-matched sibling donors...
October 2, 2017: Bone Marrow Transplantation
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