Intestinal Cell News Volume 4.33 | Aug 31 2018

TOP STORY

A Map of Toll-Like Receptor Expression in the Intestinal Epithelium Reveals Distinct Spatial, Cell Type-Specific, and Temporal Patterns

Intestinal organoid experiments revealed that toll-like receptor signaling in paneth cells or colonic intestinal epithelial cells induced a core set of host defense genes, but this set did not include antimicrobial peptides, which instead were induced indirectly by inflammatory cytokines. [Immunity] Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

Inhibition of Sodium/Hydrogen Exchanger 3 in the Gastrointestinal Tract by Tenapanor Reduces Paracellular Phosphate Permeability

Scientists found that tenapanor produced its effect by modulating tight junctions, which increased transepithelial electrical resistance (TEER) and reduced permeability to phosphate, reducing paracellular phosphate absorption. Sodium/hydrogen exchanger isoform 3 (NHE3)-deficient monolayers mimicked the phosphate phenotype of tenapanor treatment, and tenapanor did not affect TEER or phosphate flux in the absence of NHE3. [Sci Transl Med] Abstract | Press Release

Cancer Cell Adaptation to Hypoxia Involves a HIF-GPRC5A-YAP Axis

Researchers showed that G protein-coupled receptor 5A (GPRC5A) enabled hypoxic cell survival by activating the Hippo pathway effector YAP and its anti-apoptotic target gene BCL2L1. They showed that the apoptosis induced by GPRC5A depletion in hypoxia could be rescued by constitutively active YAP. [EMBO Mol Med] Full Article | Press Release | Graphical Abstract

Transcription Factor PROX1 Suppresses Notch Pathway Activation via the Nucleosome Remodeling and Deacetylase Complex in Colorectal Cancer Stem-Like Cells

Notch inhibition led to increased proliferation of PROX1-positive colorectal cancer cells but did not affect their ability to give rise to PROX1-negative secretory cells. PROX1 interacted with the nucleosome remodeling and deacetylase complex to suppress the Notch pathway. [Cancer Res] Abstract

Paneth Cells Respond to Inflammation and Contribute to Tissue Regeneration by Acquiring Stem-Like Features through SCF/c-Kit Signaling

Investigators showed that acute inflammation of the mouse small intestine was followed by a dramatic loss of Lgr5⁺ stem cells. Instead, Paneth cells re-entered the cell cycle, lost their secretory expression signature, and acquired stem-like properties, thus contributing to the tissue regenerative response to inflammation. [Cell Rep] Full Article | Graphical Abstract

Microbial Sensing by Intestinal Myeloid Cells Controls Carcinogenesis and Epithelial Differentiation

Scientists identified that decreased myeloid cell phagocytic activity promoted colon tumorigenesis. They showed that this was due to bacterial accumulation in the lamina propria and presented evidence that the underlying mechanism was bacterial induction of prostaglandin production by myeloid cells. [Cell Rep] Full Article | Graphical Abstract

Stat3 Is Indispensable for Damage-Induced Crypt Regeneration but Not for Wnt-Driven Intestinal Tumorigenesis

The regeneration of intestinal mucosa and organoid formation were significantly suppressed by signal transducer and activator of transcription 3 (Stat3) disruption, which was compensated by Wnt activation. Once organoids were recovered, Stat3 was no longer required for organoid growth. [FASEB J] Abstract

Novel β-Phenylacrylic Acid Derivatives Exert Anti-Cancer Activity by Inducing Src-Mediated Apoptosis in Wild-Type KRAS Colon Cancer

MHY791 and MHY1036 (MHYs)-induced Src/c-Jun N-terminal kinase activation which enhanced their pro-apoptotic effects and therefore inhibition of Src by the chemical inhibitor PP2 or Src siRNA abolished the response. In addition, MHYs generated reactive oxygen species and increased ER stress, and pretreatment with antioxidant-inhibited MHY-induced ER stress, Src activation, and apoptosis. [Cell Death Dis] Full Article

MALAT1-miR663a Negative Feedback Loop in Colon Cancer Cell Functions through Direct miRNA-lncRNA Binding

Both miR663a knockdown and MALAT1 activation alone significantly upregulated the expression levels of miR663a targets, including TGFB1, PIK3CD, P53, P21, and JUND, in the colon cancer cell lines HCT116 and SW480. [Cell Death Dis] Full Article

Down-Regulation of MicroRNA-214 Contributed to the Enhanced Mitochondrial Transcription Factor A and Inhibited Proliferation of Colorectal Cancer Cells

Down-regulation of mitochondrial transcription factor A inhibited nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) nuclear translocation and the expression of NF-κB depended genes. [Cell Physiol Biochem] Full Article

Subscribe to one of our other 19 science newsletters such as Pulmonary Cell News & ESC & iPSC News.

Energy Balance and Gastrointestinal Cancer: Risk, Interventions, Outcomes and Mechanisms

The current state of knowledge supports the need to better integrate mechanistic approaches with preclinical and human studies to develop effective, personalized diet and exercise interventions to reduce the burden of obesity on gastrointestinal cancer. [Nat Rev Gastroenterol Hepatol] Abstract

Potential Use of Human Stem Cell-Derived Intestinal Organoids to Study Inflammatory Bowel Diseases

The authors provide an overview of the versatility of human organoid cultures in inflammatory bowel disease (IBD) modeling. They discuss recent advances and current limitations in the application of this tool for modeling the contribution of the intestinal epithelium alone and in combination with other key cellular and molecular players in the context of IBD pathophysiology. [AAPS J] Full Article

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

Jefferson and Monell Center Sign Agreement of Cooperation

The Monell Center and Jefferson (Philadelphia University + Thomas Jefferson University) announced the signing of an Agreement of Cooperation, outlining how the two institutions will collaborate over the next year to develop joint scientific programs and clinical opportunities to advance their shared mission of improving human health. [Thomas Jefferson University] Press Release

FDA Starts Pilot to Help Sponsors Use Novel Trial Designs

The FDA has initiated a pilot program to help drug developers use complex innovative trial designs (CID). Sponsors accepted into the four-year pilot will meet twice with the FDA to discuss regulatory approaches to CID. [U.S. Food and Drug Administration (FierceBiotech)] Press Release

UCHealth Patients in Northern Colorado Step Forward to Speed Advances in Cancer Care

UCHealth Poudre Valley Hospital (UCHealth) is among the nation’s first community hospitals to collaborate with leading academic medical centers and researchers through personalized medicine consortium. The members collect and share patient data with the goal of better understanding cancer at the molecular level and more precisely assigning treatment to patients. [UCHealth] Press Release

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

Science in Iran Languishes after Trump Re-Imposes Sanctions

Over the past decade, as sanctions imposed over Iran’s nuclear program ratcheted up, Iranian scientists found creative ways to persevere. But the latest developments are inflicting heavy damage to both research programs and morale, says Hamid Gourabi, a geneticist at the Royan Institute in Tehran. [ScienceInsider] Editorial

Ethics Dumping: The Exploitative Side of Academic Research

Though many consider it to be a thing of the past, unethical and exploitative research persists in the 21st century. Researchers from high-income countries travel to resource-poor settings to undertake research that would not be allowed at home. The European commission calls this type of research “ethics dumping”. A new EU code makes equitable partnerships in resource-poor settings a condition for funding. [The Guardian] Editorial

New Research: Financial Disclosure Lacking in Publication of Clinical Trials

A substantial proportion of pharmaceutical industry payments to authors of oncology clinical trials published in major scientific journals are not disclosed, new research shows. The publications focused on clinical trials that tested new cancer drugs. The new findings were published as a research letter in the journal JAMA Oncology. [OHSU] Editorial

Yale Prof Gets Endowed Chair Four Years after Harassment Finding

Michael Simons, a Yale School of Medicine professor who was removed from a leadership post in 2014 after the university found him guilty of sexual harassment, was given an endowed professorship in the school’s cardiology department. In response, faculty members “went into an uproar,” and the school removed an online press release about Simons’s honor, Yale Daily News reported. [The Scientist] Editorial

NEW International Society for Stem Cell Research (ISSCR) 2019 Annual Meeting
June 26-29, 2019
Los Angeles, California, United States

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

NEW Postdoctoral Research Scientist – Gastrointestinal Disorder Research (Quadram Institute Bioscience)

NEW Postdoctoral Fellow – Irritable Bowel Syndrome (University of Bergen)

NEW Senior Scientific Officer – Colorectal Cancer (Cancer Research UK Beatson Institute)

PhD Student – Colorectal Cancer (German Cancer Research Center)

Postdoctoral Scholar – Intestinal Research (Penn State College of Medicine)

Postdoctoral Position – Host-Microbiome Interactions in the Gastrointestinal Tract (University of Gothenburg)

Postdoctoral Associate – Functional Genomics of Inflammatory Bowel Disease (Center for Computational and Integrative Biology)

Assistant/Associate Research Professor – Inflammatory Bowel Disease (Cedars-Sinai Inflammatory Bowel & Immunobiology Research Institute)

Postdoctoral Position – Paneth Cells (Erasmus MC Cancer Institute)

Postdoctoral Scholar – Molecular and Cell Biology (University of California, Berkeley)

Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.

Have we missed an important article or publication in Intestinal Cell News? Click here to submit!

Comments or suggestions? Submit your feedback here.