Intestinal Cell News Volume 3.10 | Mar 17 2017

TOP STORY

Mutual Reinforcement between Telomere Capping and Canonical Wnt Signaling in the Intestinal Stem Cell Niche

Scientists showed that late-generation mTR^−/− mutants experience marked downregulation of Wnt pathway genes in intestinal crypt epithelia, including crypt base columnar stem cells and Paneth cells, and in underlying stroma. The importance of these changes was revealed by rescue of crypt apoptosis and Wnt pathway gene expression upon treatment with Wnt pathway agonists. [Nat Commun] Full Article

(Ranked by impact factor of the journal)

INTESTINAL CANCERS & DISEASES

Binding of Candida albicans to Human CEACAM1 and CEACAM6 Modulates the Inflammatory Response of Intestinal Epithelial Cells

Researchers showed for the first time that a fungal pathogen binds directly to the extracellular domain of human carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), CEACAM3, CEACAM5, and CEACAM6. Binding was specific for human CEACAMs and mediated by the N-terminal IgV-like domain. [MBio] Full Article

Induction of Intestinal Stemness and Tumorigenicity by Aberrant Internalization of Commensal Non-Pathogenic E. coli

Using a constitutively invasive variant of non-pathogenic E. coli, the authors demonstrated that chronic presence of internalized E. coli leads to enhanced oncogenicity in colon cancer cells. Instead of genomic damage, the tumorigenic effect is mediated through an expansion of the cancer stem cell population, likely through dedifferentiation of lineage-committed intestinal epithelial cells. [Cell Death Dis] Full Article

PI3K/AKT-Mediated Upregulation of WDR5 Promotes Colorectal Cancer Metastasis by Directly Targeting ZNF407

The authors identified WDR5, a vital factor that regulates vertebrate development and cell self-renewal and reprogramming, as a novel prognostic marker and therapeutic target for colorectal cancer (CRC) patients. They demonstrate that WDR5 is upregulated in CRC tissues and promotes CRC metastasis both in vitro and in vivo. [Cell Death Dis] Full Article

Angiopoietin-Like 4 Mediates Colonic Inflammation by Regulating Chemokine Transcript Stability via Tristetraprolin

Researchers showed that angiopoietin-like 4 deficiency in mice exacerbated colonic inflammation induced by dextran sulfate sodium (DSS) or stearic acid. Microbiota was similar between the two genotypes prior DSS challenge. [Sci Rep] Full Article

A Novel Model of Colitis-Associated Cancer in SAMP1/YitFc Mice with Crohn’s Disease-Like Ileitis

Scientists hypothesized that SAMP1/YitFc (SAMP) mice may be more susceptible to colonic tumorigenesis due to their predisposition to inflammatory bowel disease (IBD). To test their hypothesis, they administered azoxymethane/dextran sulfate sodium to IBD-prone SAMP and their non-inflamed parental control strain, AKR mice. [PLoS One] Full Article

Timing of Developmental Reduction in Epithelial Glutathione Redox Potential Is Associated with Increased Epithelial Proliferation in the Immature Murine Intestine

Investigators showed that intestinal epithelial cellular glutathione (GSH)/ glutathione disulfide redox potential becomes increasingly reduced over the first three weeks of life. Increased intracellular GSH has been shown to drive proliferation through increased poly-ADP-ribose polymerase activity. [Pediatr Res] Abstract

INTESTINAL STEM CELL & ORGANOID RESEARCH

The ErbB3 Receptor Tyrosine Kinase Negatively Regulates Paneth Cells by PI3K-Dependent Suppression of Atoh1

Investigators tested the role of the neuregulin receptor ErbB3 in control of paneth cell (PC) differentiation and the intestinal stem cells niche. Intestinal epithelial ErbB3 knockout caused precocious appearance of PCs as early as postnatal day seven, and substantially increased the number of mature PCs in adult mouse ileum. [Cell Death Differ] Abstract

Canonical Wnt Signaling Ameliorates Aging of Intestinal Stem Cells

The authors uncovered changes in intestinal architecture, cell number, and cell composition upon aging. They identified a decline in the regenerative capacity of intestinal stem cells (ISCs) upon aging because of a decline in canonical Wnt signaling in ISCs. Changes in expression of Wnts were found in stem cells themselves and in their niche, including Paneth cells and mesenchyme. [Cell Rep] Full Article | Press Release | Graphical Abstract

Loss of T-Cell Protein Tyrosine Phosphatase in the Intestinal Epithelium Promotes Local Inflammation by Increasing Colonic Stem Cell Proliferation

To further understand how T-cell protein tyrosine phosphatase (TC-PTP) is related to inflammatory bowel diseases, scientists investigated the role of TC-PTP in maintaining the intestinal epithelial barrier using an in vivo genetic approach. Intestinal epithelial cell-specific deletion of TC-PTP was achieved in a mouse model at steady state and in the context of dextran sulphate sodium-induced colitis. [Cell Mol Immunol] Full Article

Microbiota: A Key Orchestrator of Cancer Therapy

The authors discuss the evidence for the ability of the microbiota to modulate chemotherapy, radiotherapy and immunotherapy with a focus on the microbial species involved, their mechanism of action and the possibility of targeting the microbiota to improve anticancer efficacy while preventing toxicity. [Nat Rev Cancer] Abstract

Stem Cell Therapy for Inflammatory Bowel Disease

There is a clear need for improved treatment practices in order to avoid systemic complications with medical management and surgical intervention. Stem cell therapy is emerging as a promising treatment alternative. The author reviews key basic science articles to discuss important mechanistic aspects as to why stem cell therapy may be an effective treatment strategy to bring to the bedside. [Clin Transl Gastroenterol] Full Article

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

Ferring Collaborates with ICF on Development of a Potential New Treatment for Anal Fissures with a Focus on Improving Quality of Care for IBD Patients

Ferring Pharmaceuticals and Brazil-based Instituto de Ciências Farmacêuticas (ICF) announced a research collaboration aimed at developing a mucoadhesive rectal delivery system to treat anal fissures and to improve quality of care for patients with inflammatory bowel disease (IBD). [Ferring Pharmaceuticals] Press Release

Novigenix Signs Distribution Agreement with Dr Risch Medical Laboratory to Access Swiss German Market for Colox^®, Its Blood Based Colorectal Cancer Test

Novigenix SA announced a commercialization agreement with Dr Risch Medical Laboratory for Colox, its blood test for the early detection of colorectal cancer. [Novigenix SA] Press Release

Pasteur Institute’s Scientists Make Last-Ditch Plea to Keep Their President

Following a string of failed attempts to keep their president Christian Bréchot on after he reaches the mandated retirement age, leading researchers have continued to agitate quietly in his favor — even though the institute’s board of directors has made what seems to be a final decision on the matter and is starting a search for Bréchot’s successor. [Nature News] Editorial

A Grim Budget Day for U.S. Science: Analysis and Reaction to Trump’s Plan

President Donald Trump rolled out his first budget request to Congress. It is for the 2018 fiscal year that begins on 1 October. It calls for deep cuts to some federal science agencies, and is likely to draw fierce opposition from the scientific community and many lawmakers in Congress. [ScienceInsider] Editorial

‘Zombie’ Patent Fights over Mutant Mice Return

Like a zombie that keeps on kicking, legal battles over mutant mice used for Alzheimer’s research are haunting the field once again — four years after the last round of lawsuits. In the latest case, the University of South Florida in Tampa has sued the US National Institutes of Health for authorizing the distribution of a particular type of mouse used in the field. [Nature News] Editorial

NEW 6^th China-Europe Symposium on Biomaterials in Regenerative Medicine
May 21-24, 2017
Porto, Portugal

NEW Mitochondrial Biogenesis and Dynamics in Health, Disease and Aging
May 21-26, 2017
West Palm Beach, United States

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

NEW 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 Fellowship – Cellular Mechanisms by Which Fatty Acids Are Absorbed in the Gut (UCSF – Cardiovascular Research Institute)

Research Associate – Colorectal Cancer (University of Virginia)

Gastroenterologist(s) – General and Interventional (Temple University)

Postdoctoral Fellow – Translational Intestinal Models (Johnson & Johnson Group)

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

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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