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https://www.readbyqxmd.com/read/27906177/-normalizing-the-malignant-phenotype-of-luminal-breast-cancer-cells-via-alpha-v-beta-3-integrin
#1
Hanan Abu-Tayeh, Keren Weidenfeld, Alisa Zhilin-Roth, Sagi Schif-Zuck, Sonja Thaler, Cristina Cotarelo, Tuan Z Tan, Jean P Thiery, Jeffrey E Green, Geula Klorin, Edmond Sabo, Jonathan P Sleeman, Maty Tzukerman, Dalit Barkan
Reestablishing tissue organization of breast cancer cells into acini was previously shown to override their malignant phenotype. In our study, we demonstrate that alpha(v)beta(3) integrin (Int-αvβ3), previously shown to play a role in cancer progression, promoted differentiation and growth arrest of organoids derived from luminal A breast cancer cells grown in their relevant three-dimensional microenvironment. These organoids differentiated into normal-like acini resembling a benign stage of breast tissue...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27901089/a-silac-based-method-for-quantitative-proteomic-analysis-of-intestinal-organoids
#2
Alexis Gonneaud, Christine Jones, Naomie Turgeon, Dominique Lévesque, Claude Asselin, François Boudreau, François-Michel Boisvert
Organoids have the potential to bridge 3D cell culture to tissue physiology by providing a model resembling in vivo organs. Long-term growing organoids were first isolated from intestinal crypt cells and recreated the renewing intestinal epithelial niche. Since then, this technical breakthrough was applied to many other organs, including prostate, liver, kidney and pancreas. We describe here how to apply a SILAC-based quantitative proteomic approach to measure protein expression changes in intestinal organoids under different experimental conditions...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27899814/neurogastroenterology-engineering-human-intestinal-organoids-with-a-functional-ens
#3
Katrina Ray
No abstract text is available yet for this article.
November 30, 2016: Nature Reviews. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/27889570/inhibitor-of-apoptosis-protein-1-regulates-tumor-necrosis-factor-mediated-destruction-of-intestinal-epithelial-cells
#4
Thomas Grabinger, Konstantin J Bode, Janine Demgenski, Carina Seitz, M Eugenia Delgado, Feodora Kostadinova, Cindy Reinhold, Nima Etemadi, Sabine Wilhelm, Matthias Schweinlin, Kay Hänggi, Janin Knop, Christof Hauck, Heike Walles, John Silke, Harald Wajant, Ueli Nachbur, W Wei-Lynn Wong, Thomas Brunner
BACKGROUND AND AIMS: Tumor necrosis factor (TNF) is a cytokine that promotes inflammation and contributes to pathogenesis of inflammatory bowel diseases. Unlike other cells and tissues, intestinal epithelial cells undergo rapid cell death upon exposure to TNF, by unclear mechanisms. We investigated the roles of inhibitor of apoptosis proteins (IAPs) in the regulation of TNF-induced cell death in the intestinal epithelium of mice and intestinal organoids. METHODS: RNA from cell lines and tissues and analyzed by quantitative PCR, protein levels were analyzed by immunoblot assays...
November 23, 2016: Gastroenterology
https://www.readbyqxmd.com/read/27889058/mutations-in-reep6-cause-autosomal-recessive-retinitis-pigmentosa
#5
Gavin Arno, Smriti A Agrawal, Aiden Eblimit, James Bellingham, Mingchu Xu, Feng Wang, Christina Chakarova, David A Parfitt, Amelia Lane, Thomas Burgoyne, Sarah Hull, Keren J Carss, Alessia Fiorentino, Matthew J Hayes, Peter M Munro, Ralph Nicols, Nikolas Pontikos, Graham E Holder, Chinwe Asomugha, F Lucy Raymond, Anthony T Moore, Vincent Plagnol, Michel Michaelides, Alison J Hardcastle, Yumei Li, Catherine Cukras, Andrew R Webster, Michael E Cheetham, Rui Chen
Retinitis pigmentosa (RP) is the most frequent form of inherited retinal dystrophy. RP is genetically heterogeneous and the genes identified to date encode proteins involved in a wide range of functional pathways, including photoreceptor development, phototransduction, the retinoid cycle, cilia, and outer segment development. Here we report the identification of biallelic mutations in Receptor Expression Enhancer Protein 6 (REEP6) in seven individuals with autosomal-recessive RP from five unrelated families...
November 17, 2016: American Journal of Human Genetics
https://www.readbyqxmd.com/read/27888356/intestinal-stem-cell-transplantation
#6
REVIEW
Tetsuya Nakamura, Mamoru Watanabe
Organoid technologies to expand intestinal epithelial cells are gaining increasing attention as a useful tool to investigate many aspects of intestinal epithelial biology and pathology. One important application of organoid systems would be to use intestinal epithelial cells expanded in culture for following transplantation experiments. In this article, we present a brief overview of the studies that have succeeded in generating new epithelial tissues in the surface of native intestines in mice by organoid transplantation...
November 25, 2016: Journal of Gastroenterology
https://www.readbyqxmd.com/read/27882268/long-term-culture-of-intestinal-cell-progenitors-an-overview-of-their-development-application-and-associated-technologies
#7
REVIEW
Andrew J Hollins, Lee Parry
PURPOSE OF REVIEW: Long-term culture of adult progenitor cells in 3D is a recently emerging technology that inhabits the space between 2D cell lines and organ slice culture. RECENT FINDINGS: Adaptations to defined media components in the wake of advances in ES and iPS cell culture has led to the identification of conditions that maintained intestinal cell progenitors in culture. These conditions retain cellular heterogeneity of the normal or tumour tissue, and the cultures have been shown to be genetically stable, such that substantial biobanks are being created from patient derived material...
2016: Current Pathobiology Reports
https://www.readbyqxmd.com/read/27880906/emergence-of-a-wave-of-wnt-signaling-that-regulates-lung-alveologenesis-by-controlling-epithelial-self-renewal-and-differentiation
#8
David B Frank, Tien Peng, Jarod A Zepp, Melinda Snitow, Tiffaney L Vincent, Ian J Penkala, Zheng Cui, Michael J Herriges, Michael P Morley, Su Zhou, Min Min Lu, Edward E Morrisey
Alveologenesis is the culmination of lung development and involves the correct temporal and spatial signals to generate the delicate gas exchange interface required for respiration. Using a Wnt-signaling reporter system, we demonstrate the emergence of a Wnt-responsive alveolar epithelial cell sublineage, which arises during alveologenesis, called the axin2+ alveolar type 2 cell, or AT2(Axin2). The number of AT2(Axin2) cells increases substantially during late lung development, correlating with a wave of Wnt signaling during alveologenesis...
November 22, 2016: Cell Reports
https://www.readbyqxmd.com/read/27879513/high-grade-neuroendocrine-carcinoma-of-the-lung-with-carcinoid-morphology-a-study-of-12-cases
#9
Anne Marie Quinn, Anshuman Chaturvedi, Daisuke Nonaka
Twelve lung neuroendocrine tumors with morphologic features of carcinoid tumors but with mitotic count >10/2 mm are reported. There were 7 males and 5 females, with age ranging from 56 to 78 years. Four cases were from never-smokers. All tumors showed architectural and cytomorphologic features of carcinoid tumor, including organoid nesting, insular, trabecular, or acinar growth, and tumor cells with low nucleocytoplasmic ratio, abundant cytoplasm, ovoid to round nuclei, and salt and pepper chromatin. Angulated or confluent nesting, insular or lobular growth pattern was also seen...
November 22, 2016: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/27878736/in-vitro-cyto-biocompatibility-study-of-thin-film-transistors-substrates-using-an-organotypic-culture-method
#10
Eric Leclerc, Jean-Luc Duval, Christophe Egles, Satoshi Ihida, Hiroshi Toshiyoshi, Agnès Tixier-Mita
Thin-Film-Transistors Liquid-Crystal Display has become a standard in the field of displays. However, the structure of these devices presents interest not only in that field, but also for biomedical applications. One of the key components, called here TFT substrate, is a glass substrate with a dense and large array of thousands of transparent micro-electrodes that can be considered as a large scale multi-electrode array(s). Multi-electrode array(s) are widely used for in vitro electrical investigations on neurons and brain, allowing excitation, registration, and recording of their activity...
January 2017: Journal of Materials Science. Materials in Medicine
https://www.readbyqxmd.com/read/27873093/fatty-acids-in-a-high-fat-diet-potentially-induce-gastric-parietal-cell-damage-and-metaplasia-in-mice
#11
Yuki Hirata, Takuhito Sezaki, Miwa Tamura-Nakano, Chinatsu Oyama, Teruki Hagiwara, Takamasa Ishikawa, Shinji Fukuda, Kazuhiko Yamada, Kazuhide Higuchi, Taeko Dohi, Yuki I Kawamura
BACKGROUND: Obesity is associated with risk of adenocarcinoma in the proximal stomach. We aimed to identify the links between dietary fat and gastric premalignant lesions. METHODS: C57BL/6 mice were fed high fat diet (HFD), and gastric mucosa was histologically analysed. Morphological changes were also analysed using an electron microscope. Transcriptome analysis of purified parietal cells was performed, and non-parietal gastric corpus epithelial cells were subjected to single-cell gene-expression profiling...
November 21, 2016: Journal of Gastroenterology
https://www.readbyqxmd.com/read/27869805/engineered-human-pluripotent-stem-cell-derived-intestinal-tissues-with-a-functional-enteric-nervous-system
#12
Michael J Workman, Maxime M Mahe, Stephen Trisno, Holly M Poling, Carey L Watson, Nambirajan Sundaram, Ching-Fang Chang, Jacqueline Schiesser, Philippe Aubert, Edouard G Stanley, Andrew G Elefanty, Yuichiro Miyaoka, Mohammad A Mandegar, Bruce R Conklin, Michel Neunlist, Samantha A Brugmann, Michael A Helmrath, James M Wells
The enteric nervous system (ENS) of the gastrointestinal tract controls many diverse functions, including motility and epithelial permeability. Perturbations in ENS development or function are common, yet there is no human model for studying ENS-intestinal biology and disease. We used a tissue-engineering approach with embryonic and induced pluripotent stem cells (PSCs) to generate human intestinal tissue containing a functional ENS. We recapitulated normal intestinal ENS development by combining human-PSC-derived neural crest cells (NCCs) and developing human intestinal organoids (HIOs)...
November 21, 2016: Nature Medicine
https://www.readbyqxmd.com/read/27869803/genome-wide-crispr-screens-reveal-a-wnt-fzd5-signaling-circuit-as-a-druggable-vulnerability-of-rnf43-mutant-pancreatic-tumors
#13
Zachary Steinhart, Zvezdan Pavlovic, Megha Chandrashekhar, Traver Hart, Xiaowei Wang, Xiaoyu Zhang, Mélanie Robitaille, Kevin R Brown, Sridevi Jaksani, René Overmeer, Sylvia F Boj, Jarrett Adams, James Pan, Hans Clevers, Sachdev Sidhu, Jason Moffat, Stéphane Angers
Forward genetic screens with CRISPR-Cas9 genome editing enable high-resolution detection of genetic vulnerabilities in cancer cells. We conducted genome-wide CRISPR-Cas9 screens in RNF43-mutant pancreatic ductal adenocarcinoma (PDAC) cells, which rely on Wnt signaling for proliferation. Through these screens, we discovered a unique requirement for a Wnt signaling circuit: engaging FZD5, one of the ten Frizzled receptors encoded in the human genome. Our results uncover an underappreciated level of context-dependent specificity at the Wnt receptor level...
November 21, 2016: Nature Medicine
https://www.readbyqxmd.com/read/27869785/classic-il-6r-signalling-is-dispensable-for-intestinal-epithelial-proliferation-and-repair
#14
K Aden, A Breuer, A Rehman, H Geese, F Tran, J Sommer, G H Waetzig, T M Reinheimer, S Schreiber, S Rose-John, J Scheller, P Rosenstiel
Inflammatory bowel disease is characterized by disturbed cytokine signalling in the mucosa. Inhibition of the proinflammatory interleukin (IL)-6 pathway is a promising new therapeutic strategy, but safety concerns arise as IL-6 signalling also contributes to epithelial repair of the intestinal mucosa. To which extent IL-6 classic or trans-signalling contributes to intestinal repair remains elusive. We tested the influence of IL-6 classic signalling on intestinal repair and proliferation. Whereas IL-6 induced STAT3 phosphorylation in the colonic cancer cell lines, primary non-malignant intestinal organoids did not respond to IL-6 classic signalling...
November 21, 2016: Oncogenesis
https://www.readbyqxmd.com/read/27867006/intercellular-coupling-of-the-cell-cycle-and-circadian-clock-in-adult-stem-cell-culture
#15
Toru Matsu-Ura, Andrey Dovzhenok, Eitaro Aihara, Jill Rood, Hung Le, Yan Ren, Andrew E Rosselot, Tongli Zhang, Choogon Lee, Karl Obrietan, Marshall H Montrose, Sookkyung Lim, Sean R Moore, Christian I Hong
Circadian clock-gated cell division cycles are observed from cyanobacteria to mammals via intracellular molecular connections between these two oscillators. Here we demonstrate WNT-mediated intercellular coupling between the cell cycle and circadian clock in 3D murine intestinal organoids (enteroids). The circadian clock gates a population of cells with heterogeneous cell-cycle times that emerge as 12-hr synchronized cell division cycles. Remarkably, we observe reduced-amplitude oscillations of circadian rhythms in intestinal stem cells and progenitor cells, indicating an intercellular signal arising from differentiated cells governing circadian clock-dependent synchronized cell division cycles...
November 5, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27867005/temporal-expression-of-cd184-cxcr4-and-cd171-l1cam-identifies-distinct-early-developmental-stages-of-human-retinal-ganglion-cells-in-embryonic-stem-cell-derived-retina
#16
J G Aparicio, H Hopp, A Choi, J Mandayam Comar, V C Liao, N Harutyunyan, T C Lee
Human retinal ganglion cells (RGCs) derived from pluripotent stem cells (PSCs) have anticipated value for human disease study, drug screening, and therapeutic applications; however, their full potential remains underdeveloped. To characterize RGCs in human embryonic stem cell (hESC) derived retinal organoids we examined RGC markers and surface antigen expression and made comparisons to human fetal retina. RGCs in both tissues exhibited CD184 and CD171 expression and distinct expression patterns of the RGC markers BRN3 and RBPMS...
November 17, 2016: Experimental Eye Research
https://www.readbyqxmd.com/read/27865053/neural-progenitor-cells-and-their-role-in-the-development-and-evolutionary-expansion-of-the-neocortex
#17
REVIEW
Takashi Namba, Wieland B Huttner
The evolutionary expansion of the mammalian brain, notably the neocortex, provides a platform for the higher cognitive abilities that characterize humans. Cortical expansion is accompanied by increased folding of the pial surface, which gives rise to a gyrencephalic (folded) rather than lissencephalic (unfolded) neocortex. This expansion reflects the prolonged and increased proliferation of neural stem and progenitor cells (NPCs). Distinct classes of NPCs can be distinguished based on either cell biological criteria (apical progenitors [APs], basal progenitors [BPs]) or lineage (primary progenitors and secondary progenitors)...
November 16, 2016: Wiley Interdisciplinary Reviews. Developmental Biology
https://www.readbyqxmd.com/read/27859262/functional-and-prognostic-significance-of-the-genomic-amplification-of-frizzled-receptor-6-fzd6-in-breast-cancer
#18
Gabriele Corda, Gianluca Sala, Rossano Lattanzio, Manuela Iezzi, Michele Sallese, Giorgia Fragassi, Alessia Lamolinara, Hasan Mirza, Daniela Barcaroli, Sibylle Ermler, Elisabete Silva, Hemad Yasaei, Robert F Newbold, Paola Vagnarelli, Marcella Mottolese, Pier Giorgio Natali, Letizia Perracchio, Jelmar Quist, Anita Grigoriadis, Pierfrancesco Marra, Andrew N Tutt, Mauro Piantelli, Stefano Iacobelli, Vincenzo De Laurenzi, Arturo Sala
Frizzled receptors mediate Wnt ligands' signalling, which is crucially involved in regulating tissue development, differentiation and is often deregulated in cancer. In this study we found that the Wnt receptor frizzled 6 (FZD6) is frequently amplified in breast cancer, with an increased incidence in the triple negative breast cancer (TNBC) subtype. Ablation of FZD6 gene expression in mammary cancer cell lines: a) inhibited motility and invasion b) induced a more symmetric shape of organoid 3D cultures c) inhibited bone and liver metastasis in vivo...
November 9, 2016: Journal of Pathology
https://www.readbyqxmd.com/read/27856615/epigenetic-regulation-of-intestinal-stem-cells-by-tet1-mediated-dna-hydroxymethylation
#19
Rinho Kim, Karyn L Sheaffer, Inchan Choi, Kyoung-Jae Won, Klaus H Kaestner
Methylated cytosines are associated with gene silencing. The ten-eleven translocation (TET) hydroxylases, which oxidize methylated cytosines to 5-hydroxymethylcytosine (5hmC), are essential for cytosine demethylation. Gene silencing and activation are critical for intestinal stem cell (ISC) maintenance and differentiation, but the potential role of TET hydroxylases in these processes has not yet been examined. Here, we generated genome-wide maps of the 5hmC mark in ISCs and their differentiated progeny. Genes with high levels of hydroxymethylation in ISCs are strongly associated with Wnt signaling and developmental processes...
November 17, 2016: Genes & Development
https://www.readbyqxmd.com/read/27856416/regulation-and-function-of-bone-morphogenetic-protein-signaling-in-colonic-injury-and-inflammation
#20
Tuo Ji, Hidehiko Takabayashi, Maria Mao, Xu Han, Xiang Xue, Jennifer C Brazil, Kathryn A Eaton, Yatrik M Shah, Andrea Todisco
The bone morphogenetic proteins (BMPs) regulate gastrointestinal homeostasis. We investigated the expression of BMP-4 and the localization and function of BMP signaling during colonic injury and inflammation. Wild type mice and mice expressing the β-galactosidase (β-gal) gene under the control of a BMP responsive element (BRE), BMP-4-β-gal/+ mice, and animals generated by crossing villin-Cre mice to mice with floxed alleles of BMP receptor 1A (villin-Cre;Bmpr1a(flox/flox)), were treated with DSS to induce colonic injury and inflammation...
November 17, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
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