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Stem cell intestinal

Julia M Fraile, Diana Campos-Iglesias, Francisco Rodríguez, Yaiza Español, José M P Freije
Ubiquitin-Specific Proteases (USPs) are deubiquitinating enzymes frequently deregulated in human malignancies. Here, we show that USP54 is overexpressed in intestinal stem cells and demonstrate that its downregulation in colorectal carcinoma cells impedes tumorigenesis. We have generated mutant mice deficient for this deubiquitinase, which are viable and fertile, and protected against chemically-induced colorectal carcinoma. Furthermore, we show that USP54 is upregulated in human colon cancer and associates with poor prognosis...
October 19, 2016: Oncotarget
Yaohong Wang, Sudeep P George, Swati Roy, Eric Pham, Amin Esmaeilniakooshkghazi, Seema Khurana
In the small intestine, epithelial cells are derived from stem cells in the crypts, migrate up the villus as they differentiate and are ultimately shed from the villus tips. This process of proliferation and shedding is tightly regulated to maintain the intestinal architecture and tissue homeostasis. Apoptosis regulates both the number of stem cells in the crypts as well as the sloughing of cells from the villus tips. Previously, we have shown that villin, an epithelial cell-specific actin-binding protein functions as an anti-apoptotic protein in the gastrointestinal epithelium...
October 21, 2016: Scientific Reports
Patrick Aghajanian, Shigeo Takashima, Manash Paul, Amelia Younossi-Hartenstein, Volker Hartenstein
The visceral musculature of the Drosophila intestine plays important roles in digestion as well as development. Detailed studies investigating the embryonic development of the visceral muscle exist; comparatively little is known about postembryonic development and metamorphosis of this tissue. In this study we have combined the use of specific markers with electron microscopy to follow the formation of the adult visceral musculature and its involvement in gut development during metamorphosis. Unlike the adult somatic musculature, which is derived from a pool of undifferentiated myoblasts, the visceral musculature of the adult is a direct descendant of the larval fibers, as shown by activating a lineage tracing construct in the larval muscle and obtaining labeled visceral fibers in the adult...
October 17, 2016: Developmental Biology
Li Lu, Menglin Wu, Longhao Sun, Weidong Li, Weihua Fu, Xuening Zhang, Tong Liu
BACKGROUND: In recent years, CD44 and CD133 have been identified as 2 common used cancer stem cell (CSC) markers in gastric cancer. However, the clinicopathological and prognostic value of these markers in gastric cancer remains controversial; moreover, there is lack of comparison of these 2 markers' roles in clinical applications. A systematic review and meta-analysis was conducted to elucidate these markers' clinicopathological features and association with prognosis in patients with gastric cancer...
October 2016: Medicine (Baltimore)
Yulong Tao, Sang Zhu, Hong Yang, Fei Huang, Hui Fu, Xia Tao
Here, we provide a protocol for reliable isolation and subculture of putative mesenchymal stem cells from mice colons. This method provides a good approach to cultivate and characterize putative colonic mesenchymal stem cells (cMSCs). A high purity of cMSCs can be obtained according to this protocol. The whole isolation processes of cMSCs take about 2 h with two important digestion steps involved. Only with common culture medium, maturation of cMSCs in culture proceeds approximately 2 weeks to allow relevant researches to be conducted...
October 18, 2016: Cytotechnology
Monica D Prakash, Sarah Miller, Sarron Randall-Demllo, Kulmira Nurgali
Cancer development is often associated with chronic inflammation. To date, research into inflammation-induced cancer has largely focused on chemokines, cytokines, and their downstream targets. These inflammatory mediators may promote tumor growth, invasion, metastasis, and facilitate angiogenesis. However, the exact mechanisms by which inflammation promotes neoplasia remain unclear. Inflammatory bowel disease (IBD) is characterized by recurrent, idiopathic intestinal inflammation, the complications of which are potentially fatal...
November 2016: Inflammatory Bowel Diseases
Yaser Atlasi, Rubina Noori, Ivana Marolin, Patrick Franken, Joana Brandao, Katharina Biermann, Paola Collini, Mariam Grigorian, Eugene Lukanidin, Noona Ambartsumian, Riccardo Fodde
INTRODUCTION: S100a4 is a calcium-binding protein belonging to the family of S100-proteins, highly expressed in different stromal cell types. S100A4 has been reported as a prognostic marker in colorectal cancer in association with tumour progression and metastasis. METHODS: In this study, we analysed the in vivo role of S100a4 in intestinal tumour initiation and progression using different transgenic and knockout mouse models. RESULTS: We found that genetic ablation or overexpression of S100a4 in both Apc- and Smad4-mutant mice do not affect tumour initiation in the intestinal tract...
October 14, 2016: European Journal of Cancer
Hyun Sook Hong, Dae Yeon Hwang, Ju Hyeong Park, Suna Kim, Eun Jung Seo, Youngsook Son
Intestinal inflammation alters immune responses in the mucosa and destroys colon architecture, leading to serious diseases such as inflammatory bowel disease (IBD). Thus, regulation of inflammation is regarded as the ultimate therapy for intestinal disease. Substance-P (SP) is known to mediate proliferation, migration, and cellular senescence in a variety of cells. SP was found to mobilize stem cells from bone marrow to the site of injury and to suppress inflammatory responses by inducing regulatory T cells (Tregs) and M2 macrophages...
October 14, 2016: Cytokine
Wakana Ohashi, Shunsuke Kimura, Toshihiko Iwanaga, Yukihiro Furusawa, Tarou Irié, Hironori Izumi, Takashi Watanabe, Atsushi Hijikata, Takafumi Hara, Osamu Ohara, Haruhiko Koseki, Toshiro Sato, Sylvie Robine, Hisashi Mori, Yuichi Hattori, Hiroshi Watarai, Kenji Mishima, Hiroshi Ohno, Koji Hase, Toshiyuki Fukada
Zinc transporters play a critical role in spatiotemporal regulation of zinc homeostasis. Although disruption of zinc homeostasis has been implicated in disorders such as intestinal inflammation and aberrant epithelial morphology, it is largely unknown which zinc transporters are responsible for the intestinal epithelial homeostasis. Here, we show that Zrt-Irt-like protein (ZIP) transporter ZIP7, which is highly expressed in the intestinal crypt, is essential for intestinal epithelial proliferation. Mice lacking Zip7 in intestinal epithelium triggered endoplasmic reticulum (ER) stress in proliferative progenitor cells, leading to significant cell death of progenitor cells...
October 2016: PLoS Genetics
Subhrajit Saha, Evelyn Aranda, Yoku Hayakawa, Payel Bhanja, Safinur Atay, N Patrik Brodin, Jiufeng Li, Samuel Asfaha, Laibin Liu, Yagnesh Tailor, Jinghang Zhang, Andrew K Godwin, Wolfgang A Tome, Timothy C Wang, Chandan Guha, Jeffrey W Pollard
WNT/β-catenin signalling is crucial for intestinal homoeostasis. The intestinal epithelium and stroma are the major source of WNT ligands but their origin and role in intestinal stem cell (ISC) and epithelial repair remains unknown. Macrophages are a major constituent of the intestinal stroma. Here, we analyse the role of macrophage-derived WNT in intestinal repair in mice by inhibiting their release using a macrophage-restricted ablation of Porcupine, a gene essential for WNT synthesis. Such Porcn-depleted mice have normal intestinal morphology but are hypersensitive to radiation injury in the intestine compared with wild-type (WT) littermates...
October 13, 2016: Nature Communications
Stefan Thiem, Moritz F Eissmann, Emma Stuart, Joachim Elzer, Anna Jonas, Michael Buchert, Matthias Ernst
Temporal and spatial regulation of genes mediated by tissue-specific promoters and conditional gene expression systems provide a powerful tool to study gene function in health, disease and during development. Although transgenic mice expressing the Cre recombinase in the gastric epithelium have been reported, there is a lack of models that allow inducible and reversible gene modification in the stomach. Here, we exploited the gastrointestinal epithelium-specific expression pattern of the three trefoil factor (Tff) genes and bacterial artificial chromosome transgenesis to generate a novel mouse strain that expresses the CreERT2 recombinase and the reverse tetracycline transactivator (rtTA)...
October 12, 2016: Genesis: the Journal of Genetics and Development
Emilie Bessède, Silvia Molina, Luis Acuña Amador, Pierre Dubus, Cathy Staedel, Lucie Chambonnier, Alice Buissonnière, Elodie Sifré, Alban Giese, Lucie Bénéjat, Benoît Rousseau, Pierre Costet, David B Sacks, Francis Mégraud, Christine Varon
Helicobacter pylori infection is responsible for gastric carcinogenesis but host factors are also implicated. IQGAP1, a scaffolding protein of the adherens junctions interacting with E-cadherin, regulates cellular plasticity and proliferation. In mice, IQGAP1 deficiency leads to gastric hyperplasia. The aim of this study was to elucidate the consequences of IQGAP1 deletion on H. pylori-induced gastric carcinogenesis.Transgenic mice deleted for iqgap1 and WT littermates were infected with Helicobacter sp., and histopathological analyses of the gastric mucosa were performed...
October 6, 2016: Oncotarget
Alana M Chin, Yu-Hwai Tsai, Stacy R Finkbeiner, Melinda S Nagy, Emily M Walker, Nicole J Ethen, Bart O Williams, Michele A Battle, Jason R Spence
Much of our understanding about how intestinal stem and progenitor cells are regulated comes from studying the late fetal stages of development and the adult intestine. In this light, little is known about intestine development prior to the formation of stereotypical villus structures with columnar epithelium, a stage when the epithelium is pseudostratified and appears to be a relatively uniform population of progenitor cells with high proliferative capacity. Here, we investigated a role for WNT/β-CATENIN signaling during the pseudostratified stages of development (E13...
October 6, 2016: Stem Cell Reports
Eva Martini, Evelyn Schneider, Clemens Neufert, Markus F Neurath, Christoph Becker
As an inhibitor of apoptosis (IAP) family member, Survivin is known for its role during regulation of apoptosis. More recently its function as a cell cycle regulator has become evident. Survivin was shown to play a pivotal role during embryonic development and is highly expressed in regenerative tissue as well as in many cancer types. We examined the function of Survivin during mouse intestinal organogenesis and in gut pathophysiology. We found high expression of Survivin in experimentally induced colon cancer in mice but also in colon tumors of humans...
October 7, 2016: Cell Cycle
Fangkun Liu, Jing Huang, Bo Ning, Zhixiong Liu, Shen Chen, Wei Zhao
Patient-derived cell lines and animal models have proven invaluable for the understanding of human intestinal diseases and for drug development although both inherently comprise disadvantages and caveats. Many genetically determined intestinal diseases occur in specific tissue microenvironments that are not adequately modeled by monolayer cell culture. Likewise, animal models incompletely recapitulate the complex pathologies of intestinal diseases of humans and fall short in predicting the effects of candidate drugs...
2016: Frontiers in Pharmacology
Inês Rolim, Rita Vale Rodrigues, António Bettencourt, Rita Barros, Vânia Camilo, António Dias Pereira, Raquel Almeida, Paula Chaves
We report a case of metaplastic columnar epithelium in the mid-esophagus in a patient with history of caustic ingestion. A cardiac-type gastric phenotype, with early signs of intestinalization, was confirmed by immunohistochemistry studies (MUC5AC, MUC6, SOX2, and CDX2). Nonmetaplastic mucosa had histologic evidence of gastroesophageal reflux. In this case, esophageal reepithelization seems to have been modulated by acidic gastroesophageal reflux, which might activate transcription factors leading to phenotypic reprogramming of the regenerative epithelium...
October 5, 2016: International Journal of Surgical Pathology
Dustin J Flanagan, Renate H M Schwab, Bang M Tran, Toby J Phesse, Elizabeth Vincan
The discovery of Lgr5 as a marker of adult stem cells meant that stem cell populations could be purified and studied in isolation. Importantly, when cultured under the appropriate conditions these stem cells form organoids in tissue culture that retain many features of the tissue of origin. The organoid cultures are accessible to genetic and biochemical manipulation, bridging the gap between in vivo mouse models and conventional tissue culture. Here we describe robust protocols to establish organoids from gastrointestinal tissues (stomach, intestine, liver) and Cre-recombinase mediated gene manipulation in vitro...
October 5, 2016: Methods in Molecular Biology
Omer H Yilmaz, Semir Beyaz
Peroxisome Proliferator-Activated Receptor delta (PPAR-δ) is a nuclear receptor transcription factor that regulates gene expression during development and disease states such as cancer. However, the precise role of PPAR-δ during tumorigenesis is not well understood. Recent data suggest that PPAR-δ may have context specific oncogenic and tumor suppressive roles depending on the tissue, cell-type, or diet-induced physiology in question. For example in the intestine, pro-obesity diets, like a high fat diet (HFD), are associated with increased colorectal cancer incidence...
October 4, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Liang Wei, Brian J Leibowitz, Xinwei Wang, Michael Epperly, Joel Greenberger, Lin Zhang, Jian Yu
Radiotherapy causes dose-limiting toxicity and long-term complications in rapidly renewing tissues, including the gastrointestinal tract. Currently, there is no FDA-approved agent for the prevention or treatment of radiation-induced intestinal injury. In this study, we have shown that PD 0332991 (PD), an FDA-approved selective inhibitor of cyclin-dependent kinase 4/6 (CDK4/6), prevents radiation-induced lethal intestinal injury in mice. Treating mice with PD or a structurally distinct CDK4/6 inhibitor prior to radiation blocked proliferation and crypt apoptosis and improved crypt regeneration...
October 4, 2016: Journal of Clinical Investigation
Francis Blokzijl, Joep de Ligt, Myrthe Jager, Valentina Sasselli, Sophie Roerink, Nobuo Sasaki, Meritxell Huch, Sander Boymans, Ewart Kuijk, Pjotr Prins, Isaac J Nijman, Inigo Martincorena, Michal Mokry, Caroline L Wiegerinck, Sabine Middendorp, Toshiro Sato, Gerald Schwank, Edward E S Nieuwenhuis, Monique M A Verstegen, Luc J W van der Laan, Jeroen de Jonge, Jan N M IJzermans, Robert G Vries, Marc van de Wetering, Michael R Stratton, Hans Clevers, Edwin Cuppen, Ruben van Boxtel
The gradual accumulation of genetic mutations in human adult stem cells (ASCs) during life is associated with various age-related diseases, including cancer. Extreme variation in cancer risk across tissues was recently proposed to depend on the lifetime number of ASC divisions, owing to unavoidable random mutations that arise during DNA replication. However, the rates and patterns of mutations in normal ASCs remain unknown. Here we determine genome-wide mutation patterns in ASCs of the small intestine, colon and liver of human donors with ages ranging from 3 to 87 years by sequencing clonal organoid cultures derived from primary multipotent cells...
October 3, 2016: Nature
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