Intestinal Cell News Volume 4.12 | Apr 6 2018

TOP STORY

In Inflamed Intestinal Tissues and Epithelial Cells, Interleukin 22 Signaling Increases Expression of H19 Long Noncoding RNA, Which Promotes Mucosal Regeneration

Researchers investigated the mechanisms by which the long non-coding RNA H19, imprinted maternally expressed transcript (H19) regulates regeneration of intestinal epithelium using cell cultures and mouse models of inflammation. [Gastroenterology] Abstract

(Ranked by impact factor of the journal)

Listeria Adhesion Protein Induces Intestinal Epithelial Barrier Dysfunction for Bacterial Translocation

Scientists showed that Listeria adhesion protein induced intestinal epithelial barrier dysfunction to promote bacterial translocation. These disruptions were attributed to the production of pro-inflammatory cytokines TNF-α and IL-6, which were observed in mice challenged with WT and isogenic strains lacking the surface invasion protein Internalin A, but not a lap^– mutant. [Cell Host Microbe] Abstract | Graphical Abstract

The Role of CSF1R-Dependent Macrophages in Control of the Intestinal Stem-Cell Niche

Investigators showed that colony-stimulating factor 1 (CSF1)-dependent macrophages influence intestinal epithelial differentiation and homeostasis. In the intestinal lamina propria CSF1R mRNA expression was restricted to macrophages which were intimately associated with the crypt epithelium, and was undetectable in paneth cells. Macrophage ablation following CSF1R blockade affected Paneth cell differentiation and lead to a reduction of Lgr5⁺ intestinal stem cells. [Nat Commun] Full Article

The Colonic Epithelium Plays an Active Role in Promoting Colitis by Shaping the Tissue Cytokine Profile

The authors identified epithelial mammalian target of rapamycin (mTOR) signaling as a potential driver of inflammation in a mouse model of colitis. A kinetic analysis of mTOR inhibition revealed that the pathway regulates epithelial differentiation, which in turn controls the cytokine milieu of the colon. Consistent with their in vivo analysis, they found that cytokine expression of organoids grown ex vivo, in the absence of bacteria and immune cells, was dependent on differentiation state. [PLoS Biol] Full Article

Lgr5⁺ Intestinal Stem Cells Reside in an Unlicensed G₁ Phase

Scientists developed a method for identifying cells in intact tissue containing DNA-bound MCM2-7. Interphase cells above the transit-amplifying compartment had no DNA-bound MCM2-7, but still expressed the MCM2-7 protein, suggesting that licensing is inhibited immediately upon differentiation. They found that most proliferative Lgr5⁺ stem cells are in an unlicensed state. [J Cell Biol] Full Article

Nutritional Control of Stem Cell Division through S-Adenosylmethionine in Drosophila Intestine

Investigators identified S-adenosylmethionine (SAM), a universal methyl donor synthesized from dietary methionine, as a critical molecule that regulates stem cell division in Drosophila midgut. Depletion of either dietary methionine or SAM synthesis reduced division rate of intestinal stem cells. [Dev Cell] Abstract | Graphical Abstract

1‐L‐MT, an IDO Inhibitor, Prevented Colitis‐Associated Cancer by Inducing CDC20 Inhibition‐Mediated Mitotic Death of Colon Cancer Cells

The authors showed that 1‐L‐MT, a canonical indoleamine 2,3‐dioxygenase (IDO) inhibitor, suppressed proliferation of human colorectal cancer cells through inducing mitotic death. [Int J Cancer] Abstract

Low-Dose Decitabine Enhances the Effect of PD-1 Blockade in Colorectal Cancer with Microsatellite Stability by Re-Modulating the Tumor Microenvironment

Investigators demonstrated that low-dose decitabine could increase the expression of immune-related genes such as major histocompatibility complex genes and cytokine-related genes as well as the number of lymphocytes at the tumor site in CT26 colorectal cancer-bearing mice. [Cell Mol Immunol] Full Article

Alterations in the p53-SOCS2 Axis Contribute to Tumor Growth in Colon Cancer

Suppressor of cytokine signaling (SOCS)2 overexpression was detected in a murine model of azoxymethane/dextran sulfate sodium-induced colitis-associated colon cancer compared to mock-treated controls. [Exp Mol Med] Full Article

Metabolomic Approach for a Rapid Identification of Natural Products with Cytotoxic Activity against Human Colorectal Cancer Cells

The authors used a rapid NMR based metabolomic approach as tool to identify secondary metabolites with anti-proliferative activity against a panel of human colorectal cancer cell lines with different mutation profiles. [Sci Rep] Full Article

Generation of Intestinal Organoids Suitable for Pharmacokinetic Studies from Human Induced Pluripotent Stem Cells

Researchers generated pharmacokinetically functional intestinal organoids from human induced pluripotent stem (iPS) cells. Human iPS cells were induced to differentiate into the hindgut and then seeded on EZSPHERE plates to generate uniform spheroids, and the floating spheroids were subsequently differentiated into intestinal organoids by using small-molecule compounds. [Drug Metab Dispos] Abstract | Full Article

Increased mtDNA Copy Number Promotes Cancer Progression by Enhancing Mitochondrial Oxidative Phosphorylation in Microsatellite-Stable Colorectal Cancer

Scientists systematically investigated the functional role of altered mitochondrial DNA copy number in the survival and metastasis of microsatellite-stable colorectal cancer cells. [Signal Transduct Target Ther] Full Article

RNA Binding Proteins in Intestinal Epithelial Biology and Colorectal Cancer

The manner in which these RNA binding proteins function in the intestine and their interactions with other pivotal pathways in colorectal cancer may provide a framework for new insights and potential therapeutic applications. [Trends Mol Med] Abstract

Integration of Sensors in Gastrointestinal Organoid Culture for Biological Analysis

The authors discuss tools to capture changes in the fluid milieu of organoid cultures both in the organoid exterior as well as the luminal side of the organoids. They also describe approaches to characterize barrier functions across the epithelial layer of the gastrointestinal organoids directly or after transferring the epithelial cells to a 2D culture format in Transwells^™ or compartmentalized microchannel devices. [Cell Mol Gastroenterol Hepatol] Abstract

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

Esperite (ESP), the Cell Factory Presents Pre-Clinical Results on the New Products of the 2^nd Generation EV’s Drugs for Treatment of Inflammatory Diseases

Esperite with its biotech company The Cell Factory has acquired from OPBG the full rights to the IP and the international patent family covering the invention and the therapeutic use of the extracellular vesicles (EV’s) products. In collaboration with Women’s and Children’s Health Department of the University of Padua, Italy they are presenting the new generation EV’s biologic drugs bio-activated with Annexin V targeting multiple inflammatory diseases, i.e. Crohn’s disease, drug resistance epilepsy, stroke. [Press release from Esperite discussing research to be presented at GISM congress, Assisi and ISEV Meeting, Barcelona] Press Release

Dr. Jason Spence shares his insights on the derivation of organoids from hPSCs. Listen Now

TiGenix and Takeda Announce Alofisel^® (Darvadstrocel) Receives Approval to Treat Complex Perianal Fistulas in Crohn’s Disease in Europe

TiGenix NV and Takeda Pharmaceutical Company Limited announced that the European Commission has approved Alofisel, previously Cx601, for the treatment of complex perianal fistulas in adult patients with nonactive/mildly active luminal Crohn’s disease, [TiGenix NV] Press Release

Immune Therapeutics, Inc. Received Minutes from FDA Meeting for Lodonal™ for the Treatment for Crohn’s Disease

Immune Therapeutics, Inc. announced that it has received minutes from the Type C meeting between Immune Therapeutics on behalf of Cytocom, the license holder, and FDA to discuss next steps in the development of IRT-103 a oral once-a-day an adjunct therapy to the standard of care for moderate to severe Crohn’s disease in adults and mild to severe in pediatric patients. [Immune Therapeutics, Inc.] Press Release

U.S. Food and Drug Administration (FDA) Accepts Bristol-Myers Squibb’s Application for Opdivo (Nivolumab) Plus Yervoy (Ipilimumab) for Previously Treated Patients with MSI-H or dMMR Metastatic Colorectal Cancer for Priority Review

Bristol-Myers Squibb company announced that the FDA accepted its supplemental Biologics License Application for Opdivo in combination with Yervoy for the treatment of adults with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. [Bristol-Myers Squibb Company] Press Release

Why The Ohio State University Decided to Go Public about Misconduct

In an unusual move, The Ohio State University in Columbus released a detailed account of the scientific misbehavior of one of its former faculty members. The 75-page report was damning: It concluded that cancer researcher Ching-Shih Chen—once lauded as an “Innovator of the Year” and the winner of millions of dollars in federal funding—had committed misconduct in eight papers. [ScienceInsider] Editorial

Unnecessary Exclusions Shut Patients Out of Clinical Trials

The FDA will hold a public meeting in Washington to discuss issues related to clinical trial eligibility criteria. Researchers, study sponsors, patients, and the general public will have an opportunity to share their experiences and tell our regulators why it’s time to revisit the guidelines. [STAT News] Editorial

French Universities Cancel Subscriptions to Springer Journals

French research organizations and universities have canceled their subscriptions to Springer journals, due to an impasse in fee negotiations between the publisher and Couperin.org, a national consortium representing more than 250 academic institutions in France. [The Scientist] Editorial

Cancer Researchers Push to Relax Rules for Clinical Trials

US government examines whether criteria for participating in drug studies unnecessarily exclude some people. [Nature News] Editorial

2018 March for Science Will Be Far More than Street Protests

The March for Science has matured. It may even have outgrown its name. [ScienceInsider] Editorial

NEW 3D Cell Culture 2018
June 5-7, 2018
Freiburg, Germany

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

NEW Postdoctoral Position – Digestive Health (University of California, Irvine)

NEW Postdoctoral Position – Inflammation and Metabolism (Sanford Burnham Prebys Medical Discovery Institute)

Postdoctoral Fellowship – Intestinal Cancer (University of Gothenburg)

Postdoctoral Research Fellow – Colon Cancer (Health Sciences North Research Institute)

Postdoctoral Research Fellow – Lysosomes in Neonatal Enterocytes and Their Pathologies (Northwestern University)

Director Position – Immune Intestinal Homeostasis (Institute for Basic Science)

Postdoctoral Fellow – Mucosal Immunology (Centre of Molecular Inflammation Research)

Postdoctoral Position – Molecular Biology/Signal Transduction/ Cancer/Inflammation (Universite de Liege)

Academic Positions – Inflammatory Bowel Disease (Cedars-Sinai Inflammatory Bowel and Immunobiology Research Institute)

Clinical Research Training Fellowship – Gastro-Intestinal Pathology with Scientific Research (University College London)

Postdoctoral Fellow – Inflammatory Bowel Disease (Marshall University)

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