Hepatic Cell News 3.35 September 27, 2019 | |
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TOP STORYModeling Human Hepato-Biliary-Pancreatic Organogenesis from the Foregut-Midgut Boundary Researchers report the continuous patterning and dynamic morphogenesis of hepatic, biliary and pancreatic structures, invaginating from a three-dimensional culture of human pluripotent stem cells. The boundary interactions between anterior and posterior gut spheroids differentiated from human pluripotent stem cells enabled retinoic acid-dependent emergence of hepato-biliary-pancreatic organ domains specified at the foregut-midgut boundary organoids in the absence of extrinsic factors. [Nature] Abstract | Press Release | |
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PUBLICATIONS(Ranked by impact factor of the journal)Using conditional depletion of liver Kupffer cells, scientists traced the developmental stages of monocytes differentiating into Kupffer cells and mapped the cellular interactions imprinting the Kupffer cell identity. Kupffer cell loss induced tumor necrosis factor- and interleukin-1 receptor-dependent activation of stellate cells and endothelial cells, resulting in the transient production of chemokines and adhesion molecules orchestrating monocyte engraftment. [Immunity] Full Article | Graphical Abstract Investigators identified Tcf21 as a novel deactivation factor of fibrogenic hepatic stellate celss (HSCs) HSCs by screening transcription factors whose expression is up-regulated in parallel to the differentiation of fetal HSCs. Expression of Tcf21 in HSCs remarkably decreased during culture-induced activation in vitro and in murine and human fibrotic liver tissue in vivo. [Hepatology] Abstract Protein Kinase C Inhibitors Override ZEB1-Induced Chemoresistance in HCC ZEB1-expressing hepatocellular cancer (HCC) cell lines became resistant to conventional chemotherapeutic agents and were enriched in CD44high/CD24low cell population. ZEB1– or TGFβ-induced epithelial-mesenchymal transition increased PKCα abundance. Probing public databases ascertained a positive association of ZEB1 and PKCα expression in human HCC tumors. [Cell Death Dis] Full Article Ectopic Parkin expression enhanced proteasome inhibitor-induced apoptosis and tumor suppression in hepatocellular cancer cells in vitro and in vivo. In contrast, knockdown of Parkin expression promoted apoptosis resistance and tumor growth. [Cell Death Dis] Full Article Induced pluripotent stem-cell-derived human hepatocytes were treated with the genotoxic carcinogens aflatoxin B1 and benzo[a]pyrene, the non-genotoxic liver carcinogen methapyrilene, and the non-carcinogens aflatoxin B2 and benzo[e]pyrene at non-cytotoxic concentrations for seven days, and transcriptomic and DNA methylation profiles were examined. [Arch Toxicol] Abstract Imaging of Hepatic Drug Transporters with [131I]6-β-Iodomethyl-19-Norcholesterol Hepatic uptake of [131I]6-β-iodomethyl-19-norcholesterol (NP-59) with and without rifampicin was evaluated using HEK293 cells expressing solute carrier transporters. The stability of NP-59 was evaluated using mouse blood, bile, and liver, and human liver S9. [Sci Rep] Full Article Researchers tested whether this chemo-preventive effect is mediated by the induction of S-adenosylmethionine (SAM) biosynthesis and its metabolic flow. SAM hepatic levels and the methionine cycle were recovered with IFC305 treatment, restoring transmethylation and transsulfuration activities. IFC305 treatment, increased MAT1a levels and decrease MAT2a levels through modulation of their post-transcriptional regulation. [Cancer Biol Ther] Abstract Scientists evaluated the therapeutic potential of human umbilical cord perivascular cells (HUCPVCs) engineered to produce Insulin Growth Factor like-I in experimental liver fibrosis and the role of extracellular vesicles (EVs) in this effect. HUCPVCs were engineered to produce human IGF-I or green fluorescence protein using adenoviruses, and EVs were isolated from their conditioned medium. [Gene Ther] Abstract Subscribe to one of our other 19 science newsletters such as Intestinal Cell News & Pancreatic Cell News. | |
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REVIEWSThe Regulation of Hepatic Fatty Acid Synthesis and Partitioning: The Effect of Nutritional State Although genetic and environmental factors have been implicated in the development of NAFLD, it remains unclear why an imbalance in these pathways begins. The regulation of fatty acid partitioning occurs at several points, including during triacylglycerol synthesis, lipid droplet formation and lipolysis. [Nat Rev Endocrinol] Abstract The authors summarize the anti-tumor effects of regorafenib in single or combined treatment in preclinical models of hepatocellular carcinoma, colorectal cancer, and gastrointestinal stromal tumors and discuss both the global and molecular effects that account for its anti-cancer properties in the clinical setting. [Exp Mol Med] Full Article Visit our reviews page to see a complete list of reviews in the hepatic cell research field. | |
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INDUSTRY NEWSEnanta Pharmaceuticals, Inc. announced topline results from its ARGON-1 Phase IIa study of EDP-305 for the treatment of non-alcoholic steatohepatitis (NASH). [Enanta Pharmaceuticals, Inc.] Press Release Hesperos, Inc. announced the University of Central Florida (UCF) and Hesperos have received the first phase of a $3.8 million milestone-based National Institutes of Health (NIH) grant for research involving the company’s human-on-a-chip system. The goal of the research is to better understand how overdosing on opiates works, their impact on multiple organs and the effect of drugs used to treat those overdose episodes including their potential toxicity to organs. [Hesperos, Inc.] Press Release | |
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POLICY NEWSNIH Reveals Its Formula for Tracking Foreign Influences The US National Institutes of Health (NIH) thinks it may have figured out how China’s foreign talents recruitment program is undermining its system for making awards and ensuring ethical behavior by its grantees. [ScienceInsider] Editorial Situation Improves Slightly for U Alaska, Major Changes Ahead Funding cuts provoke concerns about job losses, canceled research programs, and closed departments. [The Scientist] Editorial Science in India’s Kashmir Valley in Jeopardy The country’s government has imposed a communication blackout on Jammu and Kashmir, the northernmost region in India, effectively cutting off scientists and students from the rest of the world. [The Scientist] Editorial
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EVENTSNEW Cancer Epigenetics: New Mechanisms and Therapeutic Opportunities Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Research Scientist – Fibrosis (Gilead Sciences, Inc.) Research Technologist – Intestinal Stem Cell Biology (STEMCELL Technologies Inc.) Postdoctoral Researchers – Liver Diseases (Albert Einstein College of Medicine) Postdoctoral Researcher – Liver Cell-Cell Interactions (Flanders Institute for Biotechnology) Group Leader – Immunology (University Hospital Düsseldorf) Postdoctoral Researcher – Liver Disease (Albert Einstein College of Medicine) Senior Researcher – Inflammatory Diseases (Genentech, Inc.) Postdoctoral Researcher – Microbiome in IBD (GIGA-Medical Genomics Unit) Postdoctoral Fellow – Designer Probiotics (Massachusetts General Hospital) Principal Researcher – Systems Disease Biology (Boehringer Ingelheim) Research Lab Specialist – Tumor Microenvironment & Cell Behavior (University of Southern California) Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.
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