Intestinal Cell News Volume 3.12 | Mar 31 2017

TOP STORY

A Distinct Role for Lgr5⁺ Stem Cells in Primary and Metastatic Colon Cancer

Researchers demonstrated that selective leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5)⁺ cell ablation restricts primary tumor growth, but did not result in tumor regression. Instead, tumors were maintained by proliferative Lgr5⁻ cells that continuously attempted to replenish the Lgr5⁺ cancer stem cell (CSC) pool, leading to rapid re-initiation of tumor growth upon treatment cessation. Notably, CSCs were critical for the formation and maintenance of liver metastasis derived from colorectal cancers. [Nature] Abstract | Editorial

(Ranked by impact factor of the journal)

INTESTINAL CANCERS & DISEASES

Protectin D1_{n-3 DPA} and Resolvin D5_{n-3 DPA} are Effectors of Intestinal Protection

Scientists investigated the expression and functions of specialized proresolving lipid mediators (SPMs) in intestinal inflammation. Targeted liquid chromatography-tandem mass spectrometry-based metabololipidomics was used to identify SPMs from n-3 polyunsaturated fatty acids in human inflammatory bowel diseases colon biopsies, quantifying a significant up-regulation of the resolvin and protectin pathway compared with normal gut tissue. [Proc Natl Acad Sci USA] Full Article

Sedentary Lifestyle Related Exosomal Release of Hotair from Gluteal-Femoral Fat Promotes Intestinal Cell Proliferation

Investigators showed that Hotair (HOX transcript antisense RNA) is a pro-adipogenic long non-coding RNA highly expressed in gluteal-femoral fat over other fat depots. Hotair knockout in adipose tissue resulted in gluteal-femoral fat defect. Squeeze of the gluteal-femoral fat induced intestinal proliferation in wildtype mice, while not in Hotair knockout mice. [Sci Rep] Full Article

Corticosterone Activity During Early Weaning Reprograms Molecular Markers in Rat Gastric Secretory Cells

The authors used early weaning (EW) and RU486 (glucocorticoid receptor antagonist) to investigate the roles of corticosterone on differentiation of mucous neck (MNC) and zymogenic cells (ZC) in rats, and to evaluate whether effects persisted in young adults. MNC gives rise to ZC, and mucin 6, Mist1, pepsinogen a5 and pepsinogen C are produced to characterize these cells. They found that in pups, EW augmented the expression of mucins, Mist1 and pepsinogen C at mRNA and protein levels, and changed the number of MNC and ZC. [Sci Rep] Full Article

α-Lipoic Acid Prevents the Intestinal Epithelial Monolayer Damage under Heat Stress Conditions: Model Experiments in Caco-2 Cells

Under conditions of high ambient temperatures and/or strenuous exercise, humans and animals experience considerable heat stress (HS) leading among others to intestinal epithelial damage through induction of cellular oxidative stress. The authors characterized the effects of α-Lipoic Acid on HS-induced intestinal epithelial injury using an in vitro Caco-2 cell model. [Eur J Nutr] Full Article

Tetraarsenic Hexoxide Induces G2/M Arrest, Apoptosis, and Autophagy via PI3K/Akt Suppression and p38 MAPK Activation in SW620 Human Colon Cancer Cells

Scientist investigated the anti-cancer effect of tetraarsenic hexoxide (As₄O₆) on SW620 human colon cancer cells. As₄O₆ showed a dose-dependent inhibition of SW620 cells proliferation. As₄O₆ significantly increased the sub-G1 and G2/M phase population, and Annexin V-positive cells in a dose-dependent manner. G2/M arrest was concomitant with augment of p21 and reduction in cyclin B1, cell division cycle 2 expressions. [PLoS One] Full Article

Syndecan-1 Deficiency Promotes Tumor Growth in a Murine Model of Colitis-Induced Colon Carcinoma

Investigators tested the effects of syndecan-1 (Sdc1) loss on colorectal tumor development in inflammation-driven colon tumorigenesis. Utilizing a mouse model of colitis-related colon carcinoma induced by the carcinogen azoxymethane, followed by the inflammatory agent dextran sodium sulfate, they found that Sdc1 deficiency results in increased susceptibility to colitis-associated tumorigenesis. [PLoS One] Full Article

HDAC Inhibitors Show Differential Epigenetic Regulation and Cell Survival Strategies on p53 Mutant Colon Cancer Cells

Scientists explored the changes in efficacy of the four HDAC inhibitors SAHA, MS-275, valproic acid and sodium butyrate on a panel of colon cancer cell lines – HCT116, HCT116 p53-/-, HT29 and SW480. Clonogenic assays, gene profiling and epigenetic expression done on these cells pointed to p53 dependent differential activity of the four HDAC inhibitors which also elevated methylation levels in p53 mutant cell lines. [J Biomol Struct Dyn] Abstract

INTESTINAL STEM CELL & ORGANOID RESEARCH

Apc, but Not Obesity, Synergizes with PTEN to Drive Intestinal Stem Cell Tumors

Lgr5⁺-GFP mice were provided low-fat diet (LFD) or high-fat diet (HFD) for eight months and the transcriptome was evaluated in Lgr5⁺-intestinal stem cells (ISCs). For tumor studies, Lgr5⁺-GFP and Lgr5⁺-GFP Ptenflox/flox mice were tamoxifen treated to inactivate Pten in ISCs and provided LFD or HFD until 14-15 months of age. Various combinations of Lgr5⁺-ISC specific, Apc and Pten-deleted mice were generated, and evaluated for histopathology and survival. [Endocr Relat Cancer] Abstract

WRN Conditioned Media Is Sufficient for In Vitro Propagation of Intestinal Organoids from Large Farm and Small Companion Animals

The authors showed that large farm and small companion (LF/SC) enteroids propagate and expand in L-WRN conditioned media containing signaling factors Wnt3a, R-spondin-3, and Noggin (WRN). Multiple successful isolations were achieved for each species, and the growth of LF/SC enteroids was maintained to high passage number. [Biol Open] Abstract | Full Article

Disease Modeling in Stem Cell-Derived 3D Organoid Systems

The authors discuss recent advances in the application of organoids in studying cancer and hereditary diseases, as well as in the examination of host cell–microorganism interactions. [Trends Mol Med] Abstract

Contributions of Intestinal Epithelial Barriers to Health and Disease

Researchers focus on the mechanisms by which barriers are assembled, maintained, and regulated in the context of health and disease. Because of its unique challenges and extensive study, they focus on the gastrointestinal tract as an organ-specific example of the essential contributions of the paracellular barrier to life. [Exp Cell Res] Abstract

Visit our reviews page to see a complete list of reviews in the intestinal cell research field.

Introducing PROMETHEUS^® IBcause^™: Convenient All-in-One Diagnostic Test for Persistent Diarrhea

Prometheus Laboratories Inc. announced the launch of IBcause^™, an all-in-one convenient test that evaluates a unique combination of 20 stool and serum measures all at one time. IBcause will assist healthcare providers in diagnosing many common causes of persistent diarrhea. [Prometheus Laboratories Inc.] Press Release

Synergy Pharmaceuticals Submits Supplemental New Drug Application (sNDA) for TRULANCE^™ (Plecanatide) for the Treatment of Adults with Irritable Bowel Syndrome with Constipation (IBS-C)

Synergy Pharmaceuticals Inc. announced that the company has submitted a sNDA for TRULANCE^™ for the treatment of adults with IBS-C. TRULANCE was approved in the United States for the treatment of adults with chronic idiopathic constipation and is now available in U.S. pharmacies. [Synergy Pharmaceuticals Inc.] Press Release

Trump Wants 2018 NIH Cut to Come from Overhead Payments

The Trump administration could slash $5.8 billion from the 2018 budget of the National Institutes of Health, yet still fund as least as much research by eliminating overhead payments to universities and research institutions, Secretary of Health and Human Services Tom Price told lawmakers. [ScienceInsider] Editorial

European Commission Considering Leap into Open-Access Publishing

One of Europe’s biggest science spenders could soon branch out into publishing. The European Commission, which spends more than €10 billion annually on research, may follow two other big league funders, the Wellcome Trust and the Bill & Melinda Gates Foundation, and set up a “publishing platform” for the scientists it funds, in an attempt to accelerate the transition to open-access publishing in Europe. [ScienceInsider] Editorial

NEW 2^nd Bioprocessing of Advanced Cellular Therapies Congress
June 8-9, 2017
London, United Kingdom

Visit our events page to see a complete list of events in the community.

NEW Postdoctoral Fellow – Mucosal Immunology (University of North Carolina at Chapel Hill)

PhD/PhD-MD Studentship – Intestinal Immunology/Immunophathobiology (Universität Bern)

Assistant Professor – Innate and Adaptive Immune Responses to Intestinal Pathogens and the Microbiota (University of Alabama)

Postdoctoral Fellow – Epigenetics of Intestinal Stem Cells (AstraZeneca)

Postdoctoral Fellow – Intestinal Pathogens on Host Metabolism (Boston Children’s Hospital and Harvard Medical School)

Senior Scientist – Pathology of Immunology and Gastrointestinal Diseases (Takeda Pharmaceuticals)

Assistant & Associate Investigators – Colorectal, Pancreatic, Gastric and Esophageal Cancers (Baylor Scott & White Health)

Postdoctoral Fellow – Intestinal Pathogens on Host Development and Metabolism (Boston Children’s Hospital/Harvard Medical School)

Faculty Position – Intestinal Stem Cell Research (Duke University Division of Gastroenterology)

Postdoctoral Research Fellow – Intestinal Disease (Children’s Hospital Los Angeles)

Assistant or Associate Member – Stem Cell/Gene Therapy (Fred Hutchinson Cancer Research Center)

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