Intestinal Cell News Volume 4.21 | Jun 8 2018

TOP STORY

Stem-Cell Niche for 10 Billion Colon Cells a Day

Researchers have discovered the identity of the stem-cell niche of the colon. The niche comprises special cells that activate the stem cells of the adjacent intestinal epithelium and are responsible for its continuous renewal. [Press release from the University of Zurich discussing online prepublication in Nature] Press Release | Abstract

(Ranked by impact factor of the journal)

A Metabolite-Triggered Tuft Cell-ILC2 Circuit Drives Small Intestinal Remodeling

The small intestinal tuft cell-ILC2 circuit mediated epithelial responses to intestinal helminths and protists by tuft cell chemosensory-like sensing and IL-25-mediated activation of lamina propria ILC2s. Small intestine ILC2s constitutively expressed the IL-25 receptor, which is negatively regulated by A20. A20 deficiency in ILC2s spontaneously triggered the circuit and, unexpectedly, promoted adaptive small-intestinal lengthening and remodeling. [Cell] Abstract | Graphical Abstract

Paneth Cell Multipotency Induced by Notch Activation following Injury

Irradiation induced a subset of paneth cells to proliferate and differentiate into villus epithelial cells. RNA sequencing revealed that paneth cells sorted from irradiated mice acquired a stem cell-like transcriptome; when cultured in vitro, these individual paneth cells formed organoids. [Cell Stem Cell] Abstract | Graphical Abstract

An Increase in LRRK2 Suppresses Autophagy and Enhances Dectin-1-Induced Immunity in a Mouse Model of Colitis

HCT116 colon epithelial cells lacking beclin-1 exhibited increased LRRK2 expression compared to wild-type cells, suggesting that inhibition of autophagy potentially could augment LRRK2 proinflammatory signaling. LRRK2 inhibitors decreased dectin-1-induced TNF-α production by mouse dendritic cells and ameliorated dextran sodium sulfate-induced colitis, both in control and Lrrk2 transgenic animals. [Sci Transl Med] Abstract

Composite Regulation of ERK Activity Dynamics Underlying Tumor-Specific Traits in the Intestine

Investigators uncovered the extracellular signal-regulated kinase (ERK) activity dynamics in intestinal epithelial cells and their association with tumor characteristics. Activation of Wnt signaling, the earliest event in intestinal tumorigenesis, augmented EGFR signaling and increased the frequency of ERK activity pulses through controlling the expression of EGFR and its regulators, rendering intestinal epithelial cells sensitive to EGFR inhibition. [Nat Commun] Full Article

Synergistic and Low Adverse Effect Cancer Immunotherapy by Immunogenic Chemotherapy and Locally Expressed PD-L1 Trap

Scientists report the combination of immunogenic chemotherapy and locally expressed PD-L1 trap fusion protein for efficacious and safe cancer immunotherapy. They demonstrated that oxaliplatin boosts anti-PD-L1 mAb therapy against murine colorectal cancer. [Nat Commun] Full Article

Forkhead Box C1 Promotes Colorectal Cancer Metastasis through Transactivating ITGA7 and FGFR4 Expression

Using an integrated approach, researchers identified forkhead box C1 (FOXC1) as a novel regulator of colorectal cancer metastasis. Elevated expression of FOXC1 was significantly correlated with metastasis, recurrence and reduced survival. [Oncogene] Abstract

The Distinct Role of Strand-Specific miR-514b-3p and miR-514b-5p in Colorectal Cancer Metastasis

Investigators found that miR-514b-3p was significantly down-regulated in colorectal cancer (CRC) samples, and the ratio of miR-514b-3p/miR-514b-5p increased from advanced CRC, early CRC to matched normal colorectal tissues. [Cell Death Dis] Full Article

Sorting Nexin 10 Controls mTOR Activation through Regulating Amino-Acid Metabolism in Colorectal Cancer

Scientists investigated the role of sorting nexin 10 (SNX10) in regulating amino-acid metabolism and mammalian target of rapamycin (mTOR) signaling pathway activation, as well as the impact on the tumor progression of mouse colorectal cancer (CRC). Their results showed that SNX10 deficiency promoted colorectal tumorigenesis in male FVB mice and CRC cell proliferation and survival. [Cell Death Dis] Full Article

Identification of Ras-Degrading Small Molecules That Inhibit the Transformation of Colorectal Cancer Cells Independent of β-Catenin Signaling

Due to the absence of Ras degradation in cells expressing a nondegradable mutant form of β-catenin and the need to determine an alternative mechanism of Ras degradation, the authors designed a cell-based system to screen compounds that degrade Ras independent of the Wnt/β-catenin signaling pathway. [Exp Mol Med] Full Article

RAC1-GTP Promotes Epithelial-Mesenchymal Transition and Invasion of Colorectal Cancer by Activation of STAT3

Investigators demonstrated that the active form of Rac family small GTPase 1 (RAC1-GTP) is overexpressed in colorectal cancers (CRC) and promotes the epithelial-mesenchymal transition-mediated invasion of CRC cells through activation of the signal transducers and activators of transcription 3 (STAT3) pathway. [Lab Invest] Abstract

Alcohol Consumption Promotes Colorectal Carcinoma Metastasis via a CCL5-Induced and AMPK-Pathway-Mediated Activation of Autophagy

Ethanol increased the secretion of C-C chemokine ligand 5 (CCL5) in two colorectal cancer cell lines, HT29 and DLD-1. Treatment with CCL5 directly increased migratory ability of these cells, whereas neutralization or knockdown of CCL5 could partially block alcohol-stimulated migration. [Sci Rep] Full Article

Mechanically Induced Development and Maturation of Human Intestinal Organoids In Vivo

The authors showed that the incorporation of uniaxial strain, using compressed nitinol springs, in human intestinal organoids transplanted into the mesentery of mice induces growth and maturation of the organoids. [Nat Biomed Eng] Abstract

Development of an Experimental Model for Analyzing Drug Resistance in Colorectal Cancer

Colorectal cancer (CRC) is one of the most common cancers, for which combination treatment of chemotherapy is employed. However, most patients develop drug resistance during the course of treatment. To clarify the mechanisms of drug resistance, various research models have been developed. The authors introduce conventional and their established models for studying drug resistance in CRC. [Cancers] Full Article

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

Analysis of Real-World Safety Data Shows Gut-Selective Entyvio^® (Vedolizumab) Had Fewer Serious Infections and Adverse Events than Those on Systemic TNFα-Antagonist Therapy in Ulcerative Colitis and Crohn’s Disease Patients

Results of a new analysis of real-world safety data show patients given the gut-selective Takeda biologic treatment ENTYVIO^® had fewer serious infections and adverse events than those on systemic tumor necrosis factor-alpha-antagonist therapy for ulcerative colitis and Crohn’s disease. [Press release from Takeda discussing research presented at Digestive Disease Week 2018 Meeting, Washington, D.C] Press Release

New Treatment Combination Improves Outcomes for Some Patients with Colorectal Cancer

Research suggests that a new treatment combination can extend survival for many patients with advanced colorectal cancer. The findings from this study of the targeted drug nintedanib in combination with capecitabine, an approved standard therapy for colorectal cancer were presented. [Press release from Roswell Park Comprehensive Cancer Center discussing research presented at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago] Press Release

Dr. Tamara Zietek discusses the use of intestinal organoids as a model system for nutrient transport. Listen Now

New Center for Advanced Regenerative Engineering Launches

Northwestern’s newest center has officially launched with a bold mission and interdisciplinary mindset. The Center for Advanced Regenerative Engineering aims to create an ecosystem that enables researchers and clinicians to regenerate tissues and organs for adult and pediatric patients. [Northwestern University] Press Release

UT Health San Antonio Receives $24 Million NIH Research Boost

For the third time in ten years, UT Health San Antonio has garnered highly competitive National Institutes of Health (NIH) grants to speed the translation of research discovery into improved patient care. UT Health San Antonio will receive $24 million over the next five years under the Clinical and Translational Science Award Program. [UT Health San Antonio] Press Release

Go for Launch: A Former Astronaut Becomes Spain’s Science Minister

Spain has a ministry of science again—and none other than the first Spanish astronaut is leading it. The new transition government led by socialist Pedro Sánchez announced that Pedro Duque, who visited space twice, will be at the helm of the newly created Ministry for Science, Innovation, and Universities. The announcement was cheered by the Spanish scientific community, which has long suffered from declining budgets and bureaucratic hurdles. [ScienceInsider] Editorial

Scientists Fare Poorly in Super Tuesday Primary Vote

Science-minded candidates seeking seats in the next U.S. Congress took a drubbing from their Democratic opponents in a raft of primary elections across the country. [ScienceInsider] Editorial

Chile, Keen to Become a Knowledge Society, Creates a Ministry of Science

Scientists in Chile have welcomed a decision by Congress to create a science ministry. Many researchers hope that a dedicated ministry will give science more prominence and better-coordinated policies—provided the ministry’s budget matches the government’s ambitions to “bring Chile towards an information and knowledge society,” as Gonzalo Blumel, the country’s minister secretary-general of the presidency, put it in a statement issued after the 31 May vote. [ScienceInsider] Editorial

EU to World: Join Our €100-Billion Research Program

The European Commission has outlined how it plans to spend the biggest research and innovation budget in its history. In a document that sets out plans for its next major science-funding program, the Commission also confirmed new rules that will, for the first time, allow any country in the world — including a post-Brexit United Kingdom — to take part. [Nature News] Editorial

NEW The New York Stem Cell Foundation (NYSCF) Conference
October 23-24, 2018
New York, New York, United States

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

NEW Postdoctoral Fellow Position – Intestinal Research (Vanderbilt University Medical Center)

Research Technologist – Stem Cell Biology (STEMCELL Technologies Inc.)

Postdoctoral Position – Cancer Biology and Metastasis (MD Anderson Cancer Center)

Associate/Full Researcher – Cancer Biology (University of Hawaii Cancer Center)

Postdoctoral Position – Human Mucosal Immunology/Inflammatory Bowel Disease (Weill Cornell Medicine)

Postdoctoral Positions – Colon Stem Cells and Carcinogenesis (Johns Hopkins University School of Medicine)

Postdoctoral Fellowship – Inflammatory Bowel Disease (European Molecular Biology Laboratory)

Postdoctoral Position – Technology-Driven Research in Biomedicine (CeMM Research Center for Molecular Medicine)

Academic Position – Cancer Research (Cedars-Sinai Medical Center)

PhD Student – Endocrine Cells in the Gut (Helmholtz Zentrum München)

Postdoctoral Scholar – Colorectal Cancer (Medical University of South Carolina)

Postdoctoral Position – Digestive Health (University of California, Irvine)

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