Intestinal Cell News 5.07 March 1, 2019 | |
| |
TOP STORYColonic Epithelial Cell Diversity in Health and Inflammatory Bowel Disease Scientists profiled single colonic epithelial cells from patients with IBD and unaffected controls. They identified previously unknown cellular subtypes, including gradients of progenitor cells, colonocytes and goblet cells within intestinal crypts. At the top of the crypts, they found a previously unknown absorptive cell, expressing the proton channel OTOP2 and the satiety peptide uroguanylin, that senses pH and is dysregulated in inflammation and cancer. [Nature] Abstract | Press Release | |
| |
PUBLICATIONS(Ranked by impact factor of the journal)Human Colon Organoids Reveal Distinct Physiologic and Oncogenic Wnt Responses To distinguish oncogenic from physiological Wnt activity, researchers performed transcriptome and proteome profiling in isogenic human colon organoids. Culture in the presence or absence of exogenous ligand allowed them to discriminate receptor-mediated signaling from the effects of CRISPR/Cas9-induced adenoma polyposis coli loss. [J Exp Med] Abstract | Graphical Abstract Investigators showed that both excretory-secretory products and extract of T. spiralis could stimulate the release of the cytokine interleukin 25 from the mouse small intestinal villi and evoke calcium responses from tuft cells in intestinal organoids, which could be blocked by a bitter-taste receptor inhibitor, allyl isothiocyanate. [Proc Natl Acad Sci USA] Full Article Treatment with 12,13- epoxyoctadecenoic acid, which is a metabolite of cytochrome P450 monooxygenase produced from linoleic acid, increased cytokine production and JNK phosphorylation in vitro and exacerbated azoxymethane/dextran sodium sulfate-induced colon tumorigenesis in vivo. [Cancer Res] Abstract The authors identified the Wnt negative regulatory role of Sh3bp4 in the intestinal crypt. They showed that the loss of Sh3bp4 increased intestinal stem cell and paneth cell numbers in the murine intestine and accelerated adenoma development in Apcmin mice. Mechanistically, human SH3BP4 inhibited Wnt signaling downstream of β-catenin phosphorylation and ubiquitination. [Cell Rep] Full Article | Graphical Abstract Altered miR-195-5p in colon cancer cells led to distinct changes of proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). Mechanistically, miR-195-5p regulated NOTCH2 expression in a post-transcriptional manner by directly binding to 3′-UTR of the Notch2 mRNA. Subsequently, miR-195-5p/NOTCH2 suppressed GATA3-mediated IL-4 secretion in colorectal cancer cells and ultimately inhibited M2-like tumor-associated macrophage (TAM) polarization. [J Hematol Oncol] Full Article Cancer-Induced Inflammation and Inflammation-Induced Cancer in Colon: A Role for S1P Lyase Pathological crypt remodeling plus extracellular sphingosine-1-phosphate (S1P)-signaling caused delayed tumor formation characterized by S1P receptor 1, STAT3 mRNA increase, as well as programmed cell death ligand 1 expression, accompanied by a putatively counter regulatory STAT1S727 phosphorylation. [Oncogene] Abstract Cleavage of GSDME by Caspase-3 Determines Lobaplatin-Induced Pyroptosis in Colon Cancer Cells Morphologically, HT-29 and HCT116 cells treated with lobaplatin exhibited microscopic features of cell swelling and large bubbles emerging from the plasma membrane, and transmission electron microscopy revealed multiple pores in the membrane. GSDME, rather than GSDMD, was cleaved in lobaplatin-induced pyroptosis in HT-29 and HCT116 cells due to caspase-3 activation. [Cell Death Dis] Full Article Paneth Cell Granule Dynamics on Secretory Responses to Bacterial Stimuli in Enteroids Scientists report that microinjection of bacteria or lipopolysaccharide (LPS) into the enteroid lumen provided an ex vivo system for studying paneth cell secretion in real-time. The results showed that paneth cells released granules immediately when the apical surfaces of enteroid epithelial cells were exposed to LPS or live bacteria by microinjection. [Sci Rep] Full Article Intestinal organoids from wildtype-mice treated with TNF-α and IL-10- deficient-mice displayed impaired epithelial barrier with loss of membranous E-cadherin and reduced desmoglein-2 expression. These effects were counteracted by mesalamine (5-ASA) and azathioprine (AZTP). Unlike AZTP that exhibited antiproliferative effects, 5-ASA promoted wound healing in colon epithelial cells. [Sci Rep] Full Article In vitro, the CT26 and MC38 murine colon cancer cell lines were shown to upregulate IDO expression following stimulation with interferon-γ and tumor necrosis factor-α. Transfection of both cell lines with shIDO plasmid reduced IDO protein expression and function. [Cancer Gene Ther] Abstract Subscribe to one of our other 19 science newsletters such as Pulmonary Cell News & ESC & iPSC News. | |
| |
REVIEWSThe authors focus on the main cells and molecular mechanisms in IBD and how these can be targeted in order to improve intestinal barrier function and reduce inflammation. [Cells] Full Article Visit our reviews page to see a complete list of reviews in the intestinal cell research field. | |
| |
SCIENCE NEWSThese abstracts, showcase larazotide acetate’s ability to reduce permeability in an alcohol induced “leaky gut” model and further elucidate its molecular mechanism of action of renormalizing tight junctions. [Press release from Innovate Biopharmaceuticals, Inc. discussing research to be presented at the 2019 Digestive Disease Week (DDW) Conference, San Diego] Press Release The Janssen Pharmaceutical Companies of Johnson & Johnson announced 18 company-sponsored abstracts will be presented. [Press release from Janssen Global Services, LLC discussing research to be presented at the 14th Congress of the European Crohn’s and Colitis Organisation (ECCO), Copenhagen] Press Release NuCana to Present at the American Association for Cancer Research (AACR) Annual Meeting 2019 NuCana plc announced that two abstracts related to NUC-3373 were selected for presentation. NUC-3373, NuCana’s second ProTide™ in clinical development, is a transformation of the active anti-cancer metabolite of 5-fluorouracil, one of the most widely prescribed anti-cancer agents. [Press release from NuCana plc discussing research to be presented at the AACR Annual Meeting 2019, Atlanta] Press Release NOXXON to Present Latest Clinical Data from NOX-A12 / Keytruda® Combination Trial NOXXON Pharma N.V. announced that the company will present the latest safety, survival and more mature clinical data in patients treated with the CXCL12 inhibitor NOX-A12 in combination with Merck & Co./MSD’s PD-1 inhibitor Keytruda® in metastatic, microsatellite stable pancreatic and colorectal cancer patients. [Press release from NOXXON Pharma N.V. discussing research to be presented at the AACR Annual Meeting 2019, Atlanta] Press Release | |
| |
| |
INDUSTRY NEWSImmatics Announces Clinical Trial Collaboration in Immunotherapy for Solid Cancers Immatics announced a collaboration with Roche to evaluate the safety and efficacy of IMA101, Immatics’ investigational autologous cell therapy, in combination with atezolizumab, in patients with solid cancers. IMA101 is a personalized, multi-targeted investigational immunotherapy for the treatment of multiple advanced/metastatic solid tumors. [Immatics Biotechnologies GmbH] Press Release Taiho Oncology, Inc. announced that the FDA has approved LONSURF® as a treatment for adult patients with metastatic gastric or gastroesophageal junction adenocarcinoma previously treated with at least two prior lines of chemotherapy that included a fluoropyrimidine, a platinum, either a taxane or irinotecan, and if appropriate, HER2/neu-targeted therapy. [Taiho Oncology, Inc.] Press Release | |
| |
POLICY NEWSNIH Letters Asking about Undisclosed Foreign Ties Rattle U.S. Universities The National Institutes of Health (NIH) has recently sent letters to dozens of major U.S. research universities asking them to provide information about specific faculty members with NIH funding who are believed to have links to foreign governments that the Bethesda, Maryland–based institute did not know about. [ScienceInsider] Editorial Sexual Harassment Rife in Australian Science, Suggests First Workplace Survey Nearly half the female scientists who responded to an Australian survey on sexual misconduct at work have experienced sexual harassment. In a report, 10% of male scientists also said they had been sexually harassed at work. [Nature News] Editorial University of California Breaks Up With Major Publisher Over Research Access Dispute After months of negotiations, the University of California system has decided not to renew its subscriptions to journals put out by the major publisher Elsevier — a decision that could have big ripple effects for the way that academic research gets read and paid for. [STAT News] Editorial
| |
EVENTSNEW Digestive Disease Week® (DDW) Visit our events page to see a complete list of events in the community.
| |
JOB OPPORTUNITIESNEW Postdoctoral Fellow – IBD Therapeutics Research (Wellcome Sanger Instiute) PhD Research Fellowship – Pathogenesis of Celiac Disease (University of Oslo) Faculty Position- General Gastroenterology (Oregon Health and Science University) Postdoctoral Research Scientist – Intestinal Stem Cell Biology (Columbia University) Advanced Research Assistant – Inflammatory Bowel Disease Research (Wellcome Sanger Institute) Research Associate – Infections, Inflammation & Colorectal Cancer (Imperial College of London) Postdoctoral Position – Colon Cancer (Vanderbilt University) Associate Professor – Oncology (University of California, Davis) Postdoctoral Position – Paneth Cells (Erasmus MC Cancer Institute) 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. | |
|