Intestinal Cell News Volume 3.01 | Jan 13 2017

TOP STORY

Genome-Wide Association Study Identifies Distinct Genetic Contributions to Prognosis and Susceptibility in Crohn’s Disease

To better characterize how genetic variation influences disease prognosis, researchers performed a within-cases genome-wide association study in two cohorts of patients with Crohn’s disease. They identified four genome-wide significant loci, none of which showed any association with disease susceptibility. [Nat Genet] Abstract

(Ranked by impact factor of the journal)

INTESTINAL CANCERS & DISEASES

Contractile Forces at Tricellular Contacts Modulate Epithelial Organization and Monolayer Integrity

Inspired by the characterization of cellular defects in a rare EpCAM-related human intestinal disease, scientists found that the absence of EpCAM in enterocytes resulted in an aberrant apical domain. In the course of this pathological state, apical translocation towards tricellular contacts occurred with striking tight junction belt displacement. [Nat Commun] Full Article

A Paradox of Transcriptional and Functional Innate Interferon Responses of Human Intestinal Enteroids to Enteric Virus Infection

The authors infected nontransformed human intestinal enteroid cultures from multiple individuals with human rotavirus (HRV) and assessed the host epithelial response by using RNA-sequencing and functional assays. The dominant transcriptional pathway induced by HRV infection was a type III IFN-regulated response. Early after HRV infection, low levels of type III IFN protein activated IFN-stimulated genes. [Proc Natl Acad Sci USA] Abstract

miR-675-5p Supports Hypoxia Induced Epithelial to Mesenchymal Transition in Colon Cancer Cells

Researchers reported that miR-675-5p promotes glioma growth by stabilizing HIF1α; here, by use of the syngeneic cell lines they investigated the role of the miR-675-5p in colon cancer metastasis. Their results showed that miR-675-5p, over expressed in metastatic colon cancer cells, participate in tumor progression by regulating HIF1α induced epithelial to mesenchymal transition. [Oncotarget] Full Article

Expression of Ifnlr1 on Intestinal Epithelial Cells Is Critical to the Antiviral Effects of IFN-Lambda against Norovirus and Reovirus

The authors sought to identify interferon-lambda (IFN-λ) responsive cells by generation of mice with lineage-specific deletion of the receptor for IFN-λ, Ifnlr1. They found that expression of IFNLR1 on intestinal epithelial cells in the small intestine and colon was required for enteric IFN-λ antiviral activity. [J Virol] Abstract

Novel Serine 176 Phosphorylation of YBX1 Activates NF-κB in Colon Cancer

Investigators have shown that Y box protein 1 (YBX1) could function as a tumor promoter through phosphorylation of its serine 165 (S165) residue, leading to the activation of the NF-[kappa]B signaling pathway. Using mass spectrometry analysis, they discovered a quite distinct phosphorylation site, S176, on YBX1. [J Biol Chem] Abstract | Full Article

Butyrate Inhibits Cancerous HCT116 Colon Cell Proliferation but to a Lesser Extent in Noncancerous NCM460 Colon Cells

The authors hypothesize that butyrate inhibits cancerous cell proliferation but to a lesser extent in noncancerous cells through regulating apoptosis and cellular-signaling pathways. They tested this hypothesis by exposing cancerous HCT116 or non-cancerous NCM460 colon cells to physiologically relevant doses of butyrate. [Nutrients] Full Article

Spatiotemporal Modeling of Triggering and Amplifying Pathways in GLP-1 Secreting Intestinal L Cells

Investigators extended their recent model of electrical activity in primary L-cells to include spatiotemporal glucose and Ca²⁺ dynamics, and glucagon-like peptide 1 (GLP-1) secretion. The model confirmed that glucose transportation into the cell through SGLT1 cotransporters can induce Ca²⁺ influx and release of GLP-1 as a result of electrical activity, while glucose metabolism alone is insufficient to depolarize the cell and evoke GLP-1 secretion in the model, suggesting a crucial role for SGLT1 in triggering GLP-1 release in agreement with experimental studies. [Biophys J] Abstract

miR-663a Regulates Growth of Colon Cancer Cells, after Administration of Antimicrobial Peptides, by Targeting CXCR4-p21 Pathway

miR-663a was upregulated by administration of the human cathelicidin antimicrobial peptides , LL-37, and its analogue peptide, FF/CAP18, in the colon cancer cell line HCT116. Over-expression of miR-663a caused anti-proliferative effects both in vitro and in vivo. [BMC Cancer] Abstract

INTESTINAL STEM CELL & ORGANOID RESEARCH

Id2 Controls Specification of Lgr5⁺ Intestinal Stem Cell Progenitors during Gut Development

Scientists showed that the transcription regulator Id2 controls the specification of embryonic Lgr5⁺ progenitors in the developing murine small intestine. Cell fate mapping analysis revealed that Lgr5⁺ progenitors emerge at E13.5 in wild-type embryos and differ from the rest on the intestinal epithelium by a characteristic intestinal stem cell signature. [EMBO J] Abstract | Graphical Abstract

CD34⁺ Mesenchymal Cells Are a Major Component of the Intestinal Stem Cells Niche at Homeostasis and after Injury

Investigators demonstrated that CD34⁺ Gp38⁺ cells are the major intestinal producers of the niche factors Wnt2b, Gremlin1, and R-spondin1, and are sufficient to promote maintenance of Lgr5⁺ intestinal epithelial stem cells in intestinal organoids, an effect mainly mediated by Gremlin1. CD34⁺ Gp38⁺ cells developed after birth in the intestinal submucosa and expanded around the crypts during the third week of life in mice, independently of the microbiota. [Proc Natl Acad Sci USA] Abstract | Full Article

Crosstalk between Intestinal Epithelial Cell and Adaptive Immune Cell in Intestinal Mucosal Immunity

The authors make a comprehensive summary about crosstalk between intestinal epithelial cells and CD4⁺ adaptive T cells in intestinal immunity. Special attention was given to their implications in inflammatory bowel disease pathogenesis and potential therapeutic targets. [J Gastroenterol Hepatol] Abstract

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Allergan Enters into Licensing Agreement with Assembly Biosciences to Obtain Worldwide Rights to Microbiome Gastrointestinal Development Programs

Allergan plc and Assembly Biosciences, Inc. announced that Allergan has entered into a research, development, collaboration and license agreement for the worldwide rights to Assembly’s microbiome gastrointestinal development programs. The agreement provides Allergan with worldwide rights to preclinical compounds ABI-M201 and ABI-M301, targeting ulcerative colitis and Crohn’s disease, as well as two additional compounds to be identified by Assembly for irritable bowel syndromes; with diarrhea, with constipation or mixed. [Allergan plc] Press Release

FDA Grants Genentech’s Cancer Immunotherapy Tecentriq^® (Atezolizumab) Priority Review in Additional Type of Advanced Bladder Cancer

Genentech announced that the U.S. Food and Drug Administration (FDA) has accepted the company’s supplemental Biologics License Application and granted Priority Review for TECENTRIQ^® for the treatment of people with locally advanced or metastatic urothelial carcinoma who are ineligible for cisplatin chemotherapy, and are either previously untreated or have disease progression at least 12 months after receiving chemotherapy before surgery or after surgery. [Genentech] Press Release

Gates Foundation Research Can’t Be Published in Top Journals

One of the world’s most influential global health charities says that the research it funds cannot currently be published in several leading journals, because the journals do not comply with its open-access policy. [Nature News] Editorial

White House Announces Review Process for Risky Virus Studies

Federal officials released a plan to help U.S. agencies decide whether to fund controversial studies that make viruses more dangerous. The guidance may finally bring an end to a moratorium that has kept a handful of experiments funded by the Department of Health and Human Services on hold for more than two years. [ScienceInsider] Editorial

US Energy Agency Strengthens Protections for Scientists

The US Department of Energy has released new guidelines to protect researchers from political interference — a move that many say is long overdue. [Nature News] Editorial

NEW Environmental Microbial Biofilms and Human Microbiomes: Drivers of Future Sustainability
February 12-15, 2017
Singapore, Singapore

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

Research Fellow – Cross Talk between Immune Cells, Microbes and the Intestinal Barrier (University of Michigan Ann Arbor)

Project Scientist – Early Life Microbiota Interaction with the Host (Institute of Food Research)

Research Associate – Epigenetics of Human Intestinal Epithelial Cell Pathophysiology (University of Cambridge)

Assistant Professor – Gastrointestinal Health/Physiology Tenure-Track Faculty Position (University of Maryland)

Scientific Writing Associate – Literature Review/Analysis and Relevant Scientific and Medical Material (Genfit SA)

Tenure-Track Position – Various Projects (University Medical Center Utrecht)

Research Officer – Transcriptional and Epigenetic Regulation in Colon Cancer and Intestinal Development (Hudson Institute of Medical Research)

Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College)

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

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