Intestinal Cell News Volume 4.45 | Nov 23 2018

TOP STORY

Generation of Human Antral and Fundic Gastric Organoids from Pluripotent Stem Cells

The human stomach contains two primary domains: the corpus, which contains the fundic epithelium, and the antrum. Researchers detailed two protocols to differentiate human pluripotent stem cells into human gastric organoids that recapitulate both domains [Nat Protoc] Abstract

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Apoptosis of Intestinal Epithelial Cells Restricts Clostridium difficile Infection in a Model of Pseudomembranous Colitis

Investigators showed that the Pyrin inflammasome was not functional in intestinal epithelial cells (IECs) and that Pyrin signaling was dispensable for CDI-associated IEC death and for in vivo pathogenesis. [Nat Commun] Full Article | Press Release

Rotavirus VP3 Targets MAVS for Degradation to Inhibit Type III Interferon Expression in Intestinal Epithelial Cells

Researchers found that MAVS, critical for the host RNA sensing pathway upstream of interferon (IFN) induction, was degraded by the Rotavirus RNA methyl- and guanylyl-transferase (VP3) in a host-range-restricted manner. [eLife] Full Article

Efficient Generation of Small Intestinal Epithelial-Like Cells from Human iPSCs for Drug Absorption and Metabolism Studies

The small intestinal epithelial-like cells (SIECs) were efficiently generated from human induced pluripotent stem cells (hiPSCs) by treatment with WNT3A, R-spondin 3, Noggin, EGF, IGF-1, SB202190, and dexamethasone. Gene expression levels of small intestinal epithelial cell markers were similar between hiPS-SIECs and the human adult small intestine. [Stem Cell Reports] Full Article | Graphical Abstract

Spen Limits Intestinal Stem Cell Self-Renewal

Investigators demonstrated that split-ends (spen) acted at multiple points in the intestinal stem cell (ISC) lineage with an ISC-intrinsic function in controlling early commitment events of the stem cells and functioned in terminally differentiated cells to further limit the proliferation of ISCs. [PLoS Genet] Full Article

Targeting CDK7 Increases the Stability of Snail to Promote the Dissemination of Colorectal Cancer

The authors report that the expression of cyclin-dependent kinase 7 (CDK7) was upregulated in colorectal cancer (CRC) cells and tissues. THZ1 exhibited high potency and selectivity against CRC cells both in vitro and in vivo via induction of cell apoptosis rather than cell cycle disruption. [Cell Death Differ] Abstract

EPH Receptor A2 Governs a Feedback Loop That Activates Wnt/β-Catenin Signaling in Gastric Cancer

Erythropoietin-producing hepatoma (EPH) receptor A2 (EphA2) acted as a receptor for Wnt ligands and recruited axin1 to the plasma membrane by directly binding Dvl2. The EphA2-Dvl2/Axin1 interaction was enhanced by Wnt3a treatment, suggesting that EphA2 acts as a functional receptor for the Wnt/β-catenin pathway and plays a vital role in downstream signaling. [Cell Death Dis] Full Article

Long Non-Coding RNA H19 Confers 5-Fu Resistance in Colorectal Cancer by Promoting SIRT1-Mediated Autophagy

Investigators observed long non-coding RNA H19 was associated with the 5-fluorouracil (5-Fu) resistance in colorectal cancer (CRC). Quantitative analysis indicated that H19 was significantly increased in recurrent CRC patient samples. [Cell Death Dis] Full Article

A Small Molecule Approach to Degrade RAS with EGFR Repression Is a Potential Therapy for KRAS Mutation-Driven Colorectal Cancer Resistance to Cetuximab

KYA1797K suppressed the growth of tumor xenografts induced by colorectal cancer (CRC) cells as well as tumor organoids derived from CRC patients having both adenomatous polyposis coli and KRAS mutations. [Exp Mol Med] Full Article

Silibinin, A Natural Blend in Polytherapy Formulation for Targeting Cd44v6 Expressing Colon Cancer Stem Cells

A comprehensive prediction and screening of CD44v6 against 1674 lead compounds was conducted. Silibinin was identified as a potential compound targeting CD44v6. In order to substantiate these findings, the cytotoxic effect of 5FU, Silibinin and 5FU+Silibinin was assessed on human colon carcinoma cell line HCT116 derived CD44⁺ subpopulation. [Sci Rep] Full Article

An Altered Gene Expression Profile in Tyramine-Exposed Intestinal Cell Cultures Supports the Genotoxicity of This Biogenic Amine at Dietary Concentrations

The consumption of food with high concentrations of biogenic amines (BA) is discouraged by the main food safety agencies, but legal limits have only been set for histamine. The authors report a transcriptomic investigation of the oncogenic potential of the above-mentioned BA, as assessed in the HT29 human intestinal epithelial cell line. [Sci Rep] Full Article

Crosstalk between TF/FVIIa and EGFR Signaling in Colorectal Cancer Cells

Researchers detected the changes of mRNA profile in human colorectal cancer cell SW620 exposed to active coagulation factor VII (FVIIa). Microarray showed that mRNA levels of epidermal growth factor receptor (EGFR) ligands were significantly upregulated. [Cancer Biol Ther] Abstract

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Cannabis, Cannabinoids and the Endocannabinoid System – Is There Therapeutic Potential for Inflammatory Bowel Disease?

The authors synthesize the current literature surrounding the modulation of the endocannabinoid system and administration of exocannabinoids in experimental and human inflammatory bowel disease. [J Crohns Colitis] Full Article

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Theravance Biopharma Announces First Patient Dosed in Phase II Study of TD-1473 in Patients with Crohn’s Disease

Theravance Biopharma, Inc. announced dosing of the first patient in a Phase II clinical trial of TD-1473 in patients with Crohn’s disease. TD-1473 is a novel, potent, orally administered and gut-selective pan-Janus kinase inhibitor in development as a treatment for multiple inflammatory intestinal diseases. [Theravance Biopharma, Inc.] Press Release

Ipsen and 3BP Announce First Patient Dosed in Phase I/II Study for First-in-Class Radionuclide (IPN01087)

Ipsen and 3BP announced the first patient has been dosed in a Phase I/II study for the first-in-class radionuclide 177Lu-IPN01087. IPN01087 is a compound that targets cancer cells in patients with advanced solid tumors which express the neurotensin receptor subtype 1. [Ipsen] Press Release

Takeda Receives Clearance from the European Commission for the Proposed Acquisition of Shire Plc

Takeda Pharmaceutical Company Limited announced that it has received clearance from the European Commission for the proposed acquisition of Shire plc. [Takeda Pharmaceutical Company Limited] Press Release

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Australian Funding Delay Creates Stress and Uncertainty for Scientists

A weeks-long delay in a major funding announcement is having a detrimental effect on Australian science, say researchers. [Nature News] Editorial

AI Peer Reviewers Unleashed to Ease Publishing Grind

A suite of automated tools is now available to assist with peer review but humans are still in the driver’s seat. A handful of academic publishers are piloting AI tools to do anything from selecting reviewers to checking statistics and summarizing a paper’s findings. [Nature News] Editorial

NEW EMBL: Proteomics in Cell Biology and Disease Mechanisms
March 7-9, 2019
Heidelberg, Germany

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NEW Postdoctoral Research Fellowship – Mucosal Immunology (University of Oslo)

PhD Scholarship – 3D Printed Microenvironments for Mini-Organ Culture (Technical University of Denmark)

Postdoctoral Researcher – Pesticide Exposure and Effects on Colorectal Cancer (Luxembourg Institute of Health)

Postdoctoral Fellow – Organoid Modeling of Bacterial Infections (Uppsala University)

Associate Professor – Oncology (University of California, Davis)

Postdoctoral Fellow – Patient Derived Organoids (Rutgers Cancer Institute of New Jersey)

Postdoctoral Fellow – Intestinal & Colonic Stem Cell Research (Albert Einstein College of Medicine of Yeshiva University)

PhD Studentship – Gastrointestinal Adenocarcinomas (University of Cambridge)

Postdoctoral Position – Dendritic Cell Biology & Antigen Presentation (Weill Cornell Medicine)

Postdoctoral Position – Paneth Cells (Erasmus MC Cancer Institute)

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