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https://www.readbyqxmd.com/read/29235548/developmental-biology-stable-epigenetic-signatures-in-intestinal-organoids
#1
Iain Dickson
No abstract text is available yet for this article.
December 13, 2017: Nature Reviews. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/29234982/a-multicellular-model-of-intestinal-crypt-buckling-and-fission
#2
Axel A Almet, Barry D Hughes, Kerry A Landman, Inke S Näthke, James M Osborne
Crypt fission is an in vivo tissue deformation process that is involved in both intestinal homeostasis and colorectal tumourigenesis. Despite its importance, the mechanics underlying crypt fission are currently poorly understood. Recent experimental development of organoids, organ-like buds cultured from crypt stem cells in vitro, has shown promise in shedding light on crypt fission. Drawing inspiration from observations of organoid growth and fission in vivo, we develop a computational model of a deformable epithelial tissue layer...
December 12, 2017: Bulletin of Mathematical Biology
https://www.readbyqxmd.com/read/29234895/intestinal-stem-cells-to-advance-drug-development-precision-and-regenerative-medicine-a-paradigm-shift-in-translational-research
#3
Jonathan P Mochel, Albert E Jergens, Dawn Kingsbury, Hyun Jung Kim, Martín G Martín, Karin Allenspach
Recent advances in our understanding of the intestinal stem cell niche and the role of key signaling pathways on cell growth and maintenance have allowed the development of fully differentiated epithelial cells in 3D organoids. Stem cell-derived organoids carry significant levels of proteins that are natively expressed in the gut and have important roles in drug transport and metabolism. They are, therefore, particularly relevant to study the gastrointestinal (GI) absorption of oral medications. In addition, organoids have the potential to serve as a robust preclinical model for demonstrating the effectiveness of new drugs more rapidly, with more certainty, and at lower costs compared with live animal studies...
December 12, 2017: AAPS Journal
https://www.readbyqxmd.com/read/29233552/a-refined-culture-system-for-human-induced-pluripotent-stem-cell-derived-intestinal-epithelial-organoids
#4
Yu Takahashi, Shintaro Sato, Yosuke Kurashima, Tomohisa Yamamoto, Shiho Kurokawa, Yoshikazu Yuki, Naoki Takemura, Satoshi Uematsu, Chen-Yi Lai, Makoto Otsu, Hiroshi Matsuno, Hideki Osawa, Tsunekazu Mizushima, Junichi Nishimura, Mikio Hayashi, Takayuki Yamaguchi, Hiroshi Kiyono
Gut epithelial organoids are routinely used to investigate intestinal biology; however, current culture methods are not amenable to genetic manipulation, and it is difficult to generate sufficient numbers for high-throughput studies. Here, we present an improved culture system of human induced pluripotent stem cell (iPSC)-derived intestinal organoids involving four methodological advances. (1) We adopted a lentiviral vector to readily establish and optimize conditioned medium for human intestinal organoid culture...
December 1, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29226615/intestinal-organoids-containing-plga-nanoparticles-for-the-treatment-of-inflammatory-bowel-diseases
#5
Zahra Davoudi, Nathan Peroutka-Bigus, Bryan Bellaire, Michael Wannemuehler, Terrence Barrett, Balaji Narasimhan, Qun Wang
Inflammatory bowel disease (IBD) causes inflammation to the gastrointestinal tract. Local administration of Anti-inflammatory drugs such as 5-aminosalysilic acid (5-ASA) can alleviate the symptoms of IBD. The application of nanoparticles for IBD treatment in direct rectal administration showed high drug availability and treatment efficacy. However, relying on size-dependent adsorption of smaller particles is not sufficient for making the formulation capable of targeting. Intestinal organoids can improve the functionality of the nanoparticles due to their ability to adsorb small nanoparticle inside the lumen and attach to the damaged area...
December 11, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/29212456/helicobacter-induced-gastric-inflammation-alters-the-properties-of-gastric-tissue-stem-progenitor-cells
#6
Wataru Shibata, Soichiro Sue, Sachiko Tsumura, Yasuaki Ishii, Takeshi Sato, Eri Kameta, Makoto Sugimori, Hiroaki Yamada, Hiroaki Kaneko, Tomohiko Sasaki, Tomohiro Ishii, Toshihide Tamura, Masaaki Kondo, Shin Maeda
BACKGROUND: Although Helicobacter-induced gastric inflammation is the major predisposing factor for gastric carcinogenesis, the precise mechanism by which chronic gastritis causes gastric cancer remains unclear. Intestinal and spasmolytic polypeptide-expressing metaplasia (SPEM) is considered as precancerous lesions, changes in epithelial tissue stem/progenitor cells after chronic inflammation has not been clarified yet. In this study, we utilized three-dimensional gastric epithelial cell culture systems that could form organoids, mimicking gastric epithelial layer, and characterized the changes in epithelial cells after chronic Helicobacter felis infection...
December 6, 2017: BMC Gastroenterology
https://www.readbyqxmd.com/read/29212231/zbp-89-function-in-colonic-stem-cells-and-during-butyrate-induced-senescence
#7
Ramon Ocadiz-Ruiz, Amanda L Photenhauer, Michael M Hayes, Lin Ding, Eric R Fearon, Juanita L Merchant
ZBP-89 (Zfp148, ZNF148) is a Kruppel-type zinc-finger family transcription factor that binds to GC-rich DNA elements. Earlier studies in cell lines demonstrated that ZBP-89 cooperates with Wnt β-catenin signaling by inducing β-catenin gene expression. Since β-catenin levels are normally highest at the crypt base, we examined whether ZBP-89 is required for stem cell maintenance. Lineage-tracing using a Zfp148CreERT2 transgenic line demonstrated expression in both intestine and colonic stem cells. Deleting the Zfp148 locus in the colon using the Cdx2NLSCreERT2 transgene, reduced the size and number of polyps formed in the Apc-deleted mice...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29212028/non-canonical-hedgehog-signaling-is-a-positive-regulator-of-the-wnt-pathway-and-is-required-for-the-survival-of-colon-cancer-stem-cells
#8
Joseph L Regan, Dirk Schumacher, Stephanie Staudte, Andreas Steffen, Johannes Haybaeck, Ulrich Keilholz, Caroline Schweiger, Nicole Golob-Schwarzl, Dominik Mumberg, David Henderson, Hans Lehrach, Christian R A Regenbrecht, Reinhold Schäfer, Martin Lange
Colon cancer is a heterogeneous tumor driven by a subpopulation of cancer stem cells (CSCs). To study CSCs in colon cancer, we used limiting dilution spheroid and serial xenotransplantation assays to functionally define the frequency of CSCs in a panel of patient-derived cancer organoids. These studies demonstrated cancer organoids to be enriched for CSCs, which varied in frequency between tumors. Whole-transcriptome analysis identified WNT and Hedgehog signaling components to be enhanced in CSC-enriched tumors and in aldehyde dehydrogenase (ALDH)-positive CSCs...
December 5, 2017: Cell Reports
https://www.readbyqxmd.com/read/29204508/advancing-intestinal-organoid-technology-toward-regenerative%C3%A2-medicine
#9
REVIEW
Tetsuya Nakamura, Toshiro Sato
With the emergence of technologies to culture intestinal epithelial cells in vitro as various forms of intestinal organoids, there is growing interest in using such cultured intestinal cells as a source for tissue engineering and regenerative medicine. One such approach would be to combine the organoid technology with methodologies to engineer the culture environment, particularly the three-dimensional scaffold materials, to generate intestines that exquisitely recapitulate their original structures and functions...
2018: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29204504/self-renewing-monolayer-of-primary-colonic-or-rectal-epithelial-cells
#10
Yuli Wang, Matthew DiSalvo, Dulan B Gunasekara, Johanna Dutton, Angela Proctor, Michael S Lebhar, Ian A Williamson, Jennifer Speer, Riley L Howard, Nicole M Smiddy, Scott J Bultman, Christopher E Sims, Scott T Magness, Nancy L Allbritton
Background & Aims: Three-dimensional organoid culture has fundamentally changed the in vitro study of intestinal biology enabling novel assays; however, its use is limited because of an inaccessible luminal compartment and challenges to data gathering in a three-dimensional hydrogel matrix. Long-lived, self-renewing 2-dimensional (2-D) tissue cultured from primary colon cells has not been accomplished. Methods: The surface matrix and chemical factors that sustain 2-D mouse colonic and human rectal epithelial cell monolayers with cell repertoires comparable to that in vivo were identified...
July 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29198564/linking-stem-cell-function-and-growth-pattern-of-intestinal-organoids
#11
Torsten Thalheim, Marianne Quaas, Maria Herberg, Ulf-Dietrich Braumann, Christiane Kerner, Markus Loeffler, Gabriela Aust, Joerg Galle
Intestinal stem cells (ISCs) require well-defined signals from their environment in order to carry out their specific functions. Most of these signals are provided by neighboring cells that form a stem cell niche, whose shape and cellular composition self-organize. Major features of this self-organization can be studied in ISC-derived organoid culture. In this system, manipulation of essential pathways of stem cell maintenance and differentiation results in well-described growth phenotypes. We here provide an individual cell-based model of intestinal organoids that enables a mechanistic explanation of the observed growth phenotypes...
October 31, 2017: Developmental Biology
https://www.readbyqxmd.com/read/29166602/mucus-detachment-by-host-metalloprotease-meprin-%C3%AE-requires-shedding-of-its-inactive-pro-form-which-is-abrogated-by-the-pathogenic-protease-rgpb
#12
Rielana Wichert, Anna Ermund, Stefanie Schmidt, Matthias Schweinlin, Miroslaw Ksiazek, Philipp Arnold, Katharina Knittler, Frederike Wilkens, Barbara Potempa, Björn Rabe, Marit Stirnberg, Ralph Lucius, Jörg W Bartsch, Susanna Nikolaus, Maren Falk-Paulsen, Philip Rosenstiel, Marco Metzger, Stefan Rose-John, Jan Potempa, Gunnar C Hansson, Peter J Dempsey, Christoph Becker-Pauly
The host metalloprotease meprin β is required for mucin 2 (MUC2) cleavage, which drives intestinal mucus detachment and prevents bacterial overgrowth. To gain access to the cleavage site in MUC2, meprin β must be proteolytically shed from epithelial cells. Hence, regulation of meprin β shedding and activation is important for physiological and pathophysiological conditions. Here, we demonstrate that meprin β activation and shedding are mutually exclusive events. Employing ex vivo small intestinal organoid and cell culture experiments, we found that ADAM-mediated shedding is restricted to the inactive pro-form of meprin β and is completely inhibited upon its conversion to the active form at the cell surface...
November 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/29152574/human-intestinal-tract-serves-as-an-alternative-infection-route-for-middle-east-respiratory-syndrome-coronavirus
#13
Jie Zhou, Cun Li, Guangyu Zhao, Hin Chu, Dong Wang, Helen Hoi-Ning Yan, Vincent Kwok-Man Poon, Lei Wen, Bosco Ho-Yin Wong, Xiaoyu Zhao, Man Chun Chiu, Dong Yang, Yixin Wang, Rex K H Au-Yeung, Ivy Hau-Yee Chan, Shihui Sun, Jasper Fuk-Woo Chan, Kelvin Kai-Wang To, Ziad A Memish, Victor M Corman, Christian Drosten, Ivan Fan-Ngai Hung, Yusen Zhou, Suet Yi Leung, Kwok-Yung Yuen
Middle East respiratory syndrome coronavirus (MERS-CoV) has caused human respiratory infections with a high case fatality rate since 2012. However, the mode of virus transmission is not well understood. The findings of epidemiological and virological studies prompted us to hypothesize that the human gastrointestinal tract could serve as an alternative route to acquire MERS-CoV infection. We demonstrated that human primary intestinal epithelial cells, small intestine explants, and intestinal organoids were highly susceptible to MERS-CoV and can sustain robust viral replication...
November 2017: Science Advances
https://www.readbyqxmd.com/read/29144463/a-single-cell-survey-of-the-small-intestinal-epithelium
#14
Adam L Haber, Moshe Biton, Noga Rogel, Rebecca H Herbst, Karthik Shekhar, Christopher Smillie, Grace Burgin, Toni M Delorey, Michael R Howitt, Yarden Katz, Itay Tirosh, Semir Beyaz, Danielle Dionne, Mei Zhang, Raktima Raychowdhury, Wendy S Garrett, Orit Rozenblatt-Rosen, Hai Ning Shi, Omer Yilmaz, Ramnik J Xavier, Aviv Regev
Intestinal epithelial cells absorb nutrients, respond to microbes, function as a barrier and help to coordinate immune responses. Here we report profiling of 53,193 individual epithelial cells from the small intestine and organoids of mice, which enabled the identification and characterization of previously unknown subtypes of intestinal epithelial cell and their gene signatures. We found unexpected diversity in hormone-secreting enteroendocrine cells and constructed the taxonomy of newly identified subtypes, and distinguished between two subtypes of tuft cell, one of which expresses the epithelial cytokine Tslp and the pan-immune marker CD45, which was not previously associated with non-haematopoietic cells...
November 16, 2017: Nature
https://www.readbyqxmd.com/read/29142770/placental-teratoma-omphalomesenteric-duct-remnant-or-intestinal-organoid-enteroid-differentiation-a-diagnostic-dilemma
#15
Salwa Khedr, Tarek Jazaerly, Stefan Kostadinov
We report an unusual case of fully developed fetal intestinal segment(s) within a nodule on the chorionic plate of the placenta of a 27-year-old female patient at 37 weeks gestation with spontaneous vaginal delivery. Gross examination of the placenta revealed a chorionic plate nodule near the insertion of the umbilical cord, which, upon microscopic evaluation, raised the differential diagnostic possibilities of placental teratoma, vitelline/omphalomesenteric duct anomaly, and intestinal organoid differentiation...
December 2017: Journal of Pediatric Genetics
https://www.readbyqxmd.com/read/29141958/dna-methylation-defines-regional-identity-of-human-intestinal-epithelial-organoids-and-undergoes-dynamic-changes-during-development
#16
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/29130932/p120-catenin-is-an-obligate-haploinsufficient-tumor-suppressor-in-intestinal-neoplasia
#17
Sarah P Short, Jumpei Kondo, Whitney G Smalley-Freed, Haruna Takeda, Michael R Dohn, Anne E Powell, Robert H Carnahan, Mary K Washington, Manish Tripathi, D Michael Payne, Nancy A Jenkins, Neal G Copeland, Robert J Coffey, Albert B Reynolds
p120-Catenin (p120) functions as a tumor suppressor in intestinal cancer, but the mechanism is unclear. Here, using conditional p120 knockout in Apc-sensitized mouse models of intestinal cancer, we have identified p120 as an "obligatory" haploinsufficient tumor suppressor. Whereas monoallelic loss of p120 was associated with a significant increase in tumor multiplicity, loss of both alleles was never observed in tumors from these mice. Moreover, forced ablation of the second allele did not further enhance tumorigenesis, but instead induced synthetic lethality in combination with Apc loss of heterozygosity...
November 13, 2017: Journal of Clinical Investigation
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
#18
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/29116005/composite-intestinal-adenoma-microcarcinoid-in-the-colon-and-rectum-a-case-series-and-historical-review
#19
Mi-Jung Kim, Eun-Jung Lee, Do Sun Kim, Doo Han Lee, Eui Gon Youk, Hyun-Jung Kim
BACKGROUND: Composite intestinal adenoma-microcarcinoid (CIAM) is a rare colorectal lesion that mostly comprises a conventional adenomatous component with a minute proportion of neuroendocrine (NE) component. Although microcarcinoids are well-recognized in the setting of chronic inflammatory disorders of the gastrointestinal tract, large intestinal microcarcinoids associated with intestinal adenoma are exceedingly rare and their clinicopathologic characteristics are yet to be elucidated...
November 7, 2017: Diagnostic Pathology
https://www.readbyqxmd.com/read/29110754/bacterial-colonization-stimulates-a-complex-physiological-response-in-the-immature-human-intestinal-epithelium
#20
David R Hill, Sha Huang, Melinda S Nagy, Veda K Yadagiri, Courtney Fields, Dishari Mukherjee, Brooke Bons, Priya H Dedhia, Alana M Chin, Yu-Hwai Tsai, Shrikar Thodla, Thomas M Schmidt, Seth Walk, Vincent B Young, Jason R Spence
The human gastrointestinal tract is immature at birth, yet must adapt to dramatic changes such as oral nutrition and microbial colonization. The confluence of these factors can lead to severe inflammatory disease in premature infants; however, investigating complex environment-host interactions is difficult due to limited access to immature human tissue. Here, we demonstrate that the epithelium of human pluripotent stem cell-derived human intestinal organoids is globally similar to the immature human epithelium and we utilize HIOs to investigate complex host-microbe interactions in this naïve epithelium...
November 7, 2017: ELife
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