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https://www.readbyqxmd.com/read/29883265/the-enteric-microbiota-regulates-jejunal-paneth-cell-number-and-function-without-impacting-intestinal-stem-cells
#1
Alexi A Schoenborn, Richard J von Furstenberg, Smrithi Valsaraj, Farah S Hussain, Molly Stein, Michael T Shanahan, Susan J Henning, Ajay S Gulati
Paneth cells (PCs) are epithelial cells found in the small intestine, next to intestinal stem cells (ISCs) at the base of the crypts. PCs secrete antimicrobial peptides (AMPs) that regulate the commensal gut microbiota. In contrast, little is known regarding how the enteric microbiota reciprocally influences PC function. In this study, we sought to characterize the impact of the enteric microbiota on PC biology in the mouse small intestine. This was done by first enumerating jejunal PCs in germ-free (GF) versus conventionally-raised (CR) mice...
June 8, 2018: Gut Microbes
https://www.readbyqxmd.com/read/29863654/intestinal-stem-cell-isolation-and-culture-in-a-porcine-model-of-segmental-small-intestinal-ischemia
#2
Amy Stieler Stewart, John M Freund, Anthony T Blikslager, Liara M Gonzalez
Intestinal ischemia remains a major cause of morbidity and mortality in human and veterinary patients. Many disease processes result in intestinal ischemia, when the blood supply and therefore oxygen is decreased to the intestine. This leads to intestinal barrier loss and damage to the underlying tissue. Intestinal stem cells reside at the base of the crypts of Lieberkühn and are responsible for intestinal renewal during homeostasis and following injury. Ex vivo cell culture techniques have allowed for the successful study of epithelial stem cell interactions by establishing culture conditions that support the growth of three-dimensional epithelial organ-like systems (termed "enteroids" and "colonoids" from the small and large intestine, respectively)...
May 18, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29698056/the-muc2-mucin-coats-murine-paneth-cell-granules-and-facilitates-their-content-release-and-dispersion
#3
Martin Stahl, Sarah Tremblay, Marinieve Montero, Wayne Vogl, Lijun Xia, Kevan Jacobson, Alfredo Menendez, Bruce A Vallance
Paneth cells are a key subset of secretory epithelial cells found at the base of small intestinal crypts. Unlike intestinal goblet cells, which secrete the mucin Muc2, Paneth cells are best known for producing an array of antimicrobial factors. We unexpectedly identified Muc2 staining localized around Paneth cell granules. Electron microscopy (EM) confirmed an electron lucent halo around these granules, which was lost in Paneth cells from Muc2 deficient (-/- ) mice. EM as well as immunostaining for lysozyme revealed that Muc2-/- Paneth cells contained larger, more densely packed granules within their cytoplasm and we detected defects in the transcription of key antimicrobial genes in the ileal tissues of Muc2-/- mice...
April 26, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29693042/taming-the-wild-west-of-organoids-enteroids-and-mini-guts
#4
EDITORIAL
Jason R Spence
No abstract text is available yet for this article.
2018: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29675451/cftr-modulates-wnt-%C3%AE-catenin-signaling-and-stem-cell-proliferation-in-murine-intestine
#5
Ashlee M Strubberg, Jinghua Liu, Nancy M Walker, Casey D Stefanski, R John MacLeod, Scott T Magness, Lane L Clarke
Background & Aims: Cystic fibrosis (CF) patients and CF mouse models have increased risk for gastrointestinal tumors. CF mice show augmented intestinal proliferation of unknown etiology and an altered intestinal environment. We examined the role of the cystic fibrosis transmembrane conductance regulator (Cftr) in Wnt/β-catenin signaling, stem cell proliferation, and its functional expression in the active intestinal stem cell (ISC) population. Dysregulation of intracellular pH (pHi ) in CF ISCs was investigated for facilitation of Wnt/β-catenin signaling...
March 2018: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29675450/engineered-human-gastrointestinal-cultures-to-study-the-microbiome-and-infectious-diseases
#6
REVIEW
Sarah E Blutt, Sue E Crawford, Sasirekha Ramani, Winnie Y Zou, Mary K Estes
New models to study the intestine are key to understanding intestinal diseases and developing novel treatments. Intestinal organ-like culture systems (organoids and enteroids) have substantially advanced the study of the human gastrointestinal tract. Stem cell-derived cultures produce self-organizing structures that contain the multiple differentiated intestinal epithelial cell types including enterocytes, goblet, Paneth, and enteroendocrine cells. Understanding host-microbial interactions is one area in which these cultures are expediting major advancements...
March 2018: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29670862/organoid-and-enteroid-modeling-of-salmonella-infection
#7
REVIEW
Yuebang Yin, Daoguo Zhou
Salmonella are Gram-negative rod-shaped facultative anaerobic bacteria that are comprised of over 2,000 serovars. They cause gastroenteritis (salmonellosis) with headache, abdominal pain and diarrhea clinical symptoms. Salmonellosis brings a heavy burden for the public health in both developing and developed countries. Antibiotics are usually effective in treating the infected patients with severe gastroenteritis, although antibiotic resistance is on the rise. Understanding the molecular mechanisms of Salmonella infection is vital to combat the disease...
2018: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/29662124/stag2-deficiency-induces-interferon-responses-via-cgas-sting-pathway-and-restricts-virus-infection
#8
Siyuan Ding, Jonathan Diep, Ningguo Feng, Lili Ren, Bin Li, Yaw Shin Ooi, Xin Wang, Kevin F Brulois, Linda L Yasukawa, Xingnan Li, Calvin J Kuo, David A Solomon, Jan E Carette, Harry B Greenberg
Cohesin is a multi-subunit nuclear protein complex that coordinates sister chromatid separation during cell division. Highly frequent somatic mutations in genes encoding core cohesin subunits have been reported in multiple cancer types. Here, using a genome-wide CRISPR-Cas9 screening approach to identify host dependency factors and novel innate immune regulators of rotavirus (RV) infection, we demonstrate that the loss of STAG2, an important component of the cohesin complex, confers resistance to RV replication in cell culture and human intestinal enteroids...
April 16, 2018: Nature Communications
https://www.readbyqxmd.com/read/29656244/human-organoid-cultures-transformative-new-tools-for-human-virus-studies
#9
REVIEW
Sasirekha Ramani, Sue E Crawford, Sarah E Blutt, Mary K Estes
Studies of human infectious diseases have been limited by the paucity of functional models that mimic normal human physiology and pathophysiology. Recent advances in the development of multicellular, physiologically active organotypic cultures produced from embryonic and pluripotent stem cells, as well as from stem cells isolated from biopsies and surgical specimens are allowing unprecedented new studies and discoveries about host-microbe interactions. Here, we summarize recent developments in the use of organoids for studying human viral pathogens, including intestinal infections with human rotavirus, norovirus, enteroviruses and adenoviruses (intestinal organoids and enteroids), neuronal infections with Zika virus (cerebral organoids) and respiratory infections with respiratory syncytial virus in (lung bud organoids)...
April 2018: Current Opinion in Virology
https://www.readbyqxmd.com/read/29579172/micrornas-in-the-mammalian-gut-endocrine-lineage
#10
Yu-Han Hung, Praveen Sethupathy
MicroRNAs (miRNAs) are small noncoding RNA molecules that modulate gene expression at the posttranscriptional level. Numerous reports have elucidated the importance of miRNAs in the regulation of a wide array of biological processes including metabolism and energy homeostasis. miRNAs in the endocrine pancreas have been intensively studied over the last 15 years and linked to pancreatic islet development and function. In comparison, knowledge of miRNAs in gut endocrine cells, or enteroendocrine cells (EECs), is severely lacking...
February 1, 2018: Endocrinology
https://www.readbyqxmd.com/read/29553558/breast-milk-enhances-growth-of-enteroids-an-ex-vivo-model-of-cell-proliferation
#11
Wyatt E Lanik, Lily Xu, Cliff J Luke, Elise Z Hu, Pranjal Agrawal, Victoria S Liu, Rajesh Kumar, Alexa M Bolock, Congrong Ma, Misty Good
Human small intestinal enteroids are derived from the crypts and when grown in a stem cell niche contain all of the epithelial cell types. The ability to establish human enteroid ex vivo culture systems are important to model intestinal pathophysiology and to study the particular cellular responses involved. In recent years, enteroids from mice and humans are being cultured, passaged, and banked away for future use in several laboratories across the world. This enteroid platform can be used to test the effects of various treatments and drugs and what effects are exerted on different cell types in the intestine...
February 15, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29534451/stem-cell-derived-models-of-viral-infections-in-the-gastrointestinal-tract
#12
REVIEW
Wyatt E Lanik, Madison A Mara, Belgacem Mihi, Carolyn B Coyne, Misty Good
Studies on the intestinal epithelial response to viral infection have previously been limited by the absence of in vitro human intestinal models that recapitulate the multicellular complexity of the gastrointestinal tract. Recent technological advances have led to the development of "mini-intestine" models, which mimic the diverse cellular nature and physiological activity of the small intestine. Utilizing adult or embryonic intestinal tissue, enteroid and organoid systems, respectively, represent an opportunity to effectively model cellular differentiation, proliferation, and interactions that are specific to the specialized environment of the intestine...
March 10, 2018: Viruses
https://www.readbyqxmd.com/read/29533766/from-3d-organoids-back-to-2d-enteroids
#13
COMMENT
Jonathan Braverman, Ömer H Yilmaz
In this issue of Developmental Cell, Thorne et al. (2018) describe a simple, scalable method to culture 2D enteroid monolayers that surprisingly recapitulates many of the features of 3D organoid cultures and in vivo intestinal tissue and can be used for high-throughput microscopy-based experiments.
March 12, 2018: Developmental Cell
https://www.readbyqxmd.com/read/29503158/enteroid-monolayers-reveal-an-autonomous-wnt-and-bmp-circuit-controlling-intestinal-epithelial-growth-and-organization
#14
Curtis A Thorne, Ina W Chen, Laura E Sanman, Melanie H Cobb, Lani F Wu, Steven J Altschuler
The intestinal epithelium maintains a remarkable balance between proliferation and differentiation despite rapid cellular turnover. A central challenge is to elucidate mechanisms required for robust control of tissue renewal. Opposing WNT and BMP signaling is essential in establishing epithelial homeostasis. However, it has been difficult to disentangle contributions from multiple sources of morphogen signals in the tissue. Here, to dissect epithelial-autonomous morphogenic signaling circuits, we developed an enteroid monolayer culture system that recapitulates four key properties of the intestinal epithelium, namely the ability to maintain proliferative and differentiated zones, self-renew, polarize, and generate major intestinal cell types...
March 12, 2018: Developmental Cell
https://www.readbyqxmd.com/read/29467318/adenovirus-infection-of-human-enteroids-reveals-interferon-sensitivity-and-preferential-infection-of-goblet-cells
#15
Mayumi K Holly, Jason G Smith
Human adenoviruses (HAdV) are significant human pathogens. Although only a subset of HAdV serotypes commonly cause gastroenteritis in humans, most HAdV species replicate in the gastrointestinal tract. Knowledge of the complex interaction between HAdVs and the human intestinal epithelium has been limited by the lack of a suitable cell culture system containing relevant cell types. Recently, this need has been met by the stable and prolonged cultivation of primary intestinal epithelial cells as enteroids. Human enteroids have been used to reveal novel and interesting aspects of rotavirus, norovirus, and enterovirus replication, prompting us to explore their suitability for HAdV culture...
February 21, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29464078/effects-of-a-small-molecule-r-spondin-1-substitute-rs-246204-on-a-mouse-intestinal-organoid-culture
#16
Myeong-Ok Nam, Soojung Hahn, Joo Hyun Jee, Tae-Sun Hwang, Ho Yoon, Dong Hyeon Lee, Min-Soo Kwon, Jongman Yoo
Organoids, a multi-cellular and organ-like structure cultured in vitro , can be used in a variety of fields such as disease modeling, drug discovery, or cell therapy development. When organoids derived from Lgr5 stem cells are cultured ex vivo , recombinant R-spondin-1 protein should be added at a high concentration for the initiation and maintenance of the organoids. Because the addition of large amounts of R-spondin-1 greatly increases the cost of organoids, the organoids grown with R-spondin-1 are not practical for large-scale drug screening and for the development of therapeutic agents...
January 19, 2018: Oncotarget
https://www.readbyqxmd.com/read/29463660/novel-segment-and-host-specific-patterns-of-enteroaggregative-escherichia-coli-adherence-to-human-intestinal-enteroids
#17
Anubama Rajan, Lucy Vela, Xi-Lei Zeng, Xiaomin Yu, Noah Shroyer, Sarah E Blutt, Nina M Poole, Lily G Carlin, James P Nataro, Mary K Estes, Pablo C Okhuysen, Anthony W Maresso
Enteroaggregative Escherichia coli (EAEC) is an important diarrheal pathogen and a cause of both acute and chronic diarrhea. It is a common cause of pediatric bacterial diarrhea in developing countries. Despite its discovery in 1987, the intestinal tropism of the pathogen remains unknown. Cell lines used to study EAEC adherence include the HEp-2, T-84, and Caco-2 lines, but they exhibit abnormal metabolism and large variations in gene expression. Animal models either do not faithfully manifest human clinical symptoms or are cumbersome and expensive...
February 20, 2018: MBio
https://www.readbyqxmd.com/read/29438433/attempts-to-grow-human-noroviruses-a-sapovirus-and-a-bovine-norovirus-in-vitro
#18
Tomoichiro Oka, Garrett T Stoltzfus, Chelsea Zhu, Kwonil Jung, Qiuhong Wang, Linda J Saif
Noroviruses (NoVs) and Sapoviruses (SaVs) are enteric caliciviruses that have been detected in multiple mammalian species, including humans. Currently, efficient cell culture systems have been established only for murine NoVs and porcine SaV Cowden strain. Establishment of an efficient in vitro cell culture system for other NoVs and SaVs remains challenging; however, human NoV (HuNoV) replication in 3D cultured Caco-2 cells and a clone of Caco-2 cells, C2BBe1, human enteroids and in human B cells has been reported...
2018: PloS One
https://www.readbyqxmd.com/read/29433868/critical-intestinal-cells-originate-from-the-host-in-enteroid-derived-tissue-engineered-intestine
#19
Barrett P Cromeens, Yijie Wang, Yanchun Liu, Jed Johnson, Gail E Besner
BACKGROUND: Enteroid-derived tissue-engineered intestine (TEI) contains intestinal subepithelial myofibroblasts (ISEMFs) and smooth muscle cells (SMCs). However, these cell types are not present in the donor enteroids. We sought to determine the origin of these cell types and to quantify their importance in TEI development. MATERIALS AND METHODS: Crypts from pan-EGFP or LGR5-EGFP mice were used for enteroid culture and subsequent implantation for the production of TEI...
March 2018: Journal of Surgical Research
https://www.readbyqxmd.com/read/29411774/gpr43-mediates-microbiota-metabolite-scfa-regulation-of-antimicrobial-peptide-expression-in-intestinal-epithelial-cells-via-activation-of-mtor-and-stat3
#20
Ye Zhao, Feidi Chen, Wei Wu, Mingming Sun, Anthony J Bilotta, Suxia Yao, Yi Xiao, Xiangsheng Huang, Tonyia D Eaves-Pyles, George Golovko, Yuriy Fofanov, Warren D'Souza, Qihong Zhao, Zhanju Liu, Yingzi Cong
The antimicrobial peptides (AMP) produced by intestinal epithelial cells (IEC) play crucial roles in the regulation of intestinal homeostasis by controlling microbiota. Gut microbiota has been shown to promote IEC expression of RegIIIγ and certain defensins. However, the mechanisms involved are still not completely understood. In this report, we found that IEC expression levels of RegIIIγ and β-defensins 1, 3, and 4 were lower in G protein-coupled receptor (GPR)43-/- mice compared to that of wild-type (WT) mice...
February 7, 2018: Mucosal Immunology
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