Intestinal Cell News Volume 6.00 | Jan 10 2020

TOP STORY

Generation of Mesenchyme Free Intestinal Organoids from Human Induced Pluripotent Stem Cells

Using a CDX2^eGFP induced pluripotent stem cell knock-in reporter line to track the emergence of hindgut progenitors, the authors followed the kinetics of CDX2 expression throughout directed differentiation, enabling the purification of intestinal progenitors and robust generation of mesenchyme-free organoids expressing characteristic markers of small intestinal or colonic epithelium. [Nat Commun] Full Article

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Gut Stem Cell Aging Is Driven by mTORC1 via a p38 MAPK-p53 Pathway

Researchers showed that aging-caused intestinal villus structural and functional decline was regulated by mTORC1, a sensor of nutrients and growth factors, which was highly activated in intestinal stem and progenitor cells in geriatric mice. These aging phenotypes were recapitulated in intestinal stem cell-specific Tsc1 knockout mice. [Nat Commun] Full Article

Gastric Squamous-Columnar Junction Contains a Large Pool of Cancer-Prone Immature Osteopontin Responsive Lgr5^–CD44⁺ Cells

Investigators report that inactivation of tumor suppressor genes Trp53 and Rb1 in the gastric squamous-columnar junction epithelium resulted in preferential formation of metastatic poorly differentiated neoplasms, which were similar to human gastroesophageal carcinoma. [Nat Commun] Full Article

PRSS Contributes to Cetuximab Resistance in Colorectal Cancer

Researchers proved that PRSS expression levels were significantly negatively associated with the sensitivity of cancer cells to cetuximab. Detailed mechanistic analysis indicated that PRSS could cleave cetuximab, leading to resistance. [Sci Adv] Full Article

A Cell Atlas of the Adult Drosophila Midgut

The authors used single-cell RNA sequencing to characterize the transcriptome of midgut epithelial cells and identified 22 distinct clusters representing intestinal stem cells, enteroblasts, enteroendocrine cells, and enterocytes. [Proc Natl Acad Sci USA] Abstract

Innate Immune Receptor NOD2 Mediates LGR5⁺ Intestinal Stem Cell Protection Against ROS Cytotoxicity via Mitophagy Stimulation

Using irradiation as stressor and primarily murine-derived intestinal organoids as a model system, scientists showed that muramyl dipeptide induced a significant reduction of total and mitochondrial reactive oxygen species (ROS) within intestinal stem cells, which was associated with mitophagy induction. [Proc Natl Acad Sci USA] Full Article

Yap1-Driven Intestinal Repair Is Controlled by Group 3 Innate Lymphoid Cells

Scientists report that ILC3-driven epithelial proliferation and tissue regeneration were independent of IL-22. In contrast, ILC3s amplified the magnitude of Hippo-Yap1 signaling in intestinal crypt cells, ensuring adequate initiation of tissue repair and preventing excessive pathology. [Cell Rep] Full Article | Graphical Abstract

MiR-107 Confers Chemoresistance to Colorectal Cancer by Targeting Calcium-Binding Protein 39

The effects of combination treatment of dichloroacetate (DCA) and oxaliplatin were analysed both in vitro and in vivo. The DCA-responsive proteins in AMPK pathway were enriched using proteomic profiling technology. [Br J Cancer] Full Article

Dietary Fucoxanthin Induces Anoikis in Colorectal Adenocarcinoma by Suppressing Integrin Signaling in a Murine Colorectal Cancer Model

Fucoxanthin (Fx) administration significantly suppressed the incidence and multiplicity of colonic adenocarcinoma in AOM/DSS mice. A number of anoikis-like integrin β1^low/-/cleaved caspase-3^high cells in colonic adenocarcinoma and mucosal crypts were significantly increased, 8.3- and 3.5-fold in the Fx group compared with those of the control group, respectively. [J Clin Med] Full Article

Increased Stiffness of the Tumor Microenvironment in Colon Cancer Stimulates Cancer Associated Fibroblast-Mediated Prometastatic Activin a Signaling

Investigators assessed the link between biophysical forces and pro-metastatic signaling by testing the hypothesis that cancer-associated fibroblasts-generated mechanical forces lead to activin A release and associated downstream effects. They determined that stromal activin A secretion increased with increasing substrate stiffness. [Sci Rep] Full Article

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Ulcerative Colitis: Current and Emerging Treatment Strategies

Historically, medical therapy for ulcerative colitis was limited to corticosteroids. Excitingly, over the past just one to two decades, the options for medical therapy have expanded and include biologics and small molecules, with more agents actively being developed. [J Clin Med] Abstract

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

Zai Lab and Novocure Announce First Patient Enrolled in a Phase Pilot Trial of Tumor Treating Fields Together with Chemotherapy as First-Line Treatment of Gastric Cancer

Zai Lab Limited and Novocure announced that the first patient has been enrolled in a Phase II pilot clinical trial evaluating the safety and efficacy of Tumor Treating Fields in combination with chemotherapy as a first-line treatment in patients with gastric adenocarcinoma. [Zai Lab Limited] Press Release

Entrada Therapeutics Announces ENTR-501 for the Treatment of Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE)

Entrada Therapeutics, Inc. announced that it is developing ENTR-501, a novel thymidine phosphorylase enzyme replacement therapy, for the treatment of MNGIE. [Entrada Therapeutics, Inc.] Press Release

Scripps Acquires Pfizer’s Massive Microbial Library

The East Coast campus of the research institute received shipments of freeze-dried or frozen samples of more than 210,000 microbial strains, which scientists plan to mine for potentially useful natural products. [The Scientist] Editorial

Government Call for Science ‘Weirdos’ Prompts Caution from Researchers

Researchers have reacted with surprise and caution to a bizarrely worded job advertisement posted by a senior UK government adviser. The notice calls for scientists, mathematicians and “super-talented weirdos” to work for the prime minister and to help make “rapid progress with long-term problems”, and cites several scientific papers. [Nature News] Editorial

NEW Lorne Infection and Immunity Conference
February 19-21, 2020
Lorne, Australia

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

NEW Research Scientist – Inflammatory and Autoimmune Disorders (Genentech, Inc.)

NEW Postdoctoral Researcher – Immune Regulation and Stem Cells (Long Island University)

NEW Senior Scientist – Drug Concept Discovery (Boehringer Ingelheim)

Faculty Scientist Position – IBD Research (The University of Texas Health Science Center at Houston)

Postdoctoral Research Fellow – Tumor Microenvironment (Fred Hutchinson Cancer Research Center)

Researcher – Synthetic Ecology of Human Gut Microbiota (Flanders Institute for Biotechnology)

Assistant Professor – Intestinal Microbiota and Immunity (Hokkaido University)

Research Position – Microscopy of Human Tumors (Vienna University of Technology)

Research Scientist – In Vivo Research on Wnt Signaling in Self-Renewel (Surrozen)

Principal Researcher – Systems Disease Biology (Boehringer Ingelheim)

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