Intestinal Cell News Volume 1.03 | Apr 10 2015

5-Hydroxymethylcytosine Marks Promoters in Colon that Resist DNA Hypermethylation in Cancer
Researchers indicated that promoters that acquire 5-hydroxymethylcytosine (5hmC) upon normal colon differentiation are innately resistant to neoplastic hypermethylation by mechanisms that do not require high levels of 5hmC in tumors. [Genome Biol] Full Article

Systemic Organ Wasting Induced by Localized Expression of the Secreted Insulin/IGF Antagonist ImpL2
Scientists have developed a model for organ wasting in adult Drosophila, whereby overproliferation induced by activation of Yorkie, the Yap1 oncogene ortholog, in intestinal stem cells leads to wasting of the ovary, fat body, and muscle. [Dev Cell] Abstract | Graphical Abstract

Epithelial-Specific A2B Adenosine Receptor Signaling Protects the Colonic Epithelial Barrier during Acute Colitis
Researchers combined pharmacologic studies and studies in mice with global or tissue-specific deletion of the A2B adenosine receptor (Adora2b). In vitro studies with Adora2b knockdown in intestinal epithelial cultures or pharmacologic studies highlighted Adora2b-driven phosphorylation of vasodilator-stimulated phosphoprotein as a specific barrier repair response. [Mucosal Immunol] Abstract

IGF1 Stimulates Crypt Expansion via Differential Activation of Two Intestinal Stem Cell Populations
Investigators provided new evidence that insulin-like growth factor 1 (IGF1) activates two intestinal stem cell populations via distinct regulatory pathways to promote growth of normal intestinal epithelium and crypt regeneration after irradiation. [FASEB J] Abstract

Aberrant MEK5/ERK5 Signaling Contributes to Human Colon Cancer Progression via NF-κB Activation
The authors evaluated MEK5 and ERK5 expression in colon cancer progression and ascertained the relevance of MEK5/ERK5 signaling in colon cancer. [Cell Death Dis] Full Article

Pharmacologically Blocking p53-Dependent Apoptosis Protects Intestinal Stem Cells and Mice from Radiation
Using three-dimensional mouse crypt culture, scientists demonstrated that p53 target PUMA mediates radiation-induced apoptosis via a cell-intrinsic mechanism, and identified the glycogen synthase kinase 3 inhibitor CHIR99021 as a potent radioprotector. [Sci Rep] Full Article

Role of Lgr5-Positive Cells in Colorectal Cancer
To determine the role of Lgr5-positive cells in the tumorigenesis of colorectal cancers, researchers prepared an adeno-associated virus that carries diphtheria toxin fragment A under the control of the Lgr5 promoter. [Tumor Biol] Abstract

INTESTINAL STEM CELL & ORGANOID RESEARCH

Notch Receptor Regulation of Intestinal Stem Cell Homeostasis and Crypt Regeneration
The authors used genetic deletion of Notch1 and Notch2 to define receptor roles on stem cell function, cell proliferation/differentiation, and repair after injury. They observed impaired crypt regeneration after radiation in both Notch1– and Notch2-deleted intestine, suggesting that higher Notch activity is required post-injury. [Dev Biol] Abstract

Intestinal Organoids: A Model of Intestinal Fibrosis for Evaluating Anti-Fibrotic Drugs
Investigators exploited recent advances in stem cell derived human intestinal organoids as a new human model of fibrosis in Crohn’s disease. [Exp Mol Pathol] Abstract

A 3-D Enteroid-Based Model to Study T-Cell and Epithelial Cell Interaction
Scientists described a method to study T-cell-epithelial cell interactions using a recently established long-term intestinal “enteroid” culture system. [J Immunol Methods] Abstract

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BÜHLMANN Launches IBDoc^® – The First CE Marked Calprotectin Home Test
BÜHLMANN announced the launch of IBDoc^®, the first in vitro diagnostic test to measure the fecal inflammation marker calprotectin at home. [BÜHLMANN Laboratories AG] Press Release

USPTO Issues Key US Patent to TiGenix for the Use of Adipose Derived Stromal Cells in the Treatment of Fistulas
TiGenix NV announced that the United States Patent and Trademark Office (USPTO) has issued US Patent 8,999,709 relating to the use of an adipose derived stromal cell population in the treatment of fistula [TiGenix NV (GlobeNewswire, Inc.)] Press Release

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Food and Drug Administration (United States)

Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)

NEW Assistant Investigator – Colon Cancer (Baylor Research Institute and Sammons Cancer Center)

NEW Postdoctoral Research Fellow (Brigham and Women’s Hospital and the Dana-Farber Cancer Institute)

NEW Senior Medical Advisor – Inflammation & Immunology (Celgene Corporation)

NEW Research Fellows in Bioinformatics (University of Exeter)

Scientist – Pluripotent Stem Cell Biology Endoderm Lineages (STEMCELL Technologies Inc.)

Postdoctoral Fellow – Transcriptional Mechanisms of Stomach and Intestinal Stem Cells (Sickkids Research Institute)

Postdoctoral Position – Functional Role of Intestinal Macrophages (University of Massachusetts Medical School)

Postdoctoral Fellowship – New Therapies for Inflammatory Bowel Diseases (Cornell University)

Postdoctoral Positions – Microbiota in Cancer (Mount Sinai School of Medicine)

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