Hepatic Cell News Volume 3.36 | Sep 27 2019

TOP STORY

Modeling 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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Stellate Cells, Hepatocytes, and Endothelial Cells Imprint the Kupffer Cell Identity on Monocytes Colonizing the Liver Macrophage Niche

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

A Novel Deactivation Factor of Fibrogenic Hepatic Stellate Cells Induces Regression of Liver Fibrosis in Mice

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 CD44^high/CD24^low 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

Parkin Facilitates Proteasome Inhibitor-Induced Apoptosis via Suppression of NF-κB Activity in Hepatocellular Carcinoma

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

Gene Expression and Cytosine DNA Methylation Alterations in Induced Pluripotent Stem-Cell-Derived Human Hepatocytes Treated with Low Doses of Chemical Carcinogens

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

Diminished S-Adenosylmethionine Biosynthesis and Its Metabolism in a Model of Hepatocellular Carcinoma Is Recuperated by an Adenosine Derivative

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

Human Umbilical Cord Perivascular Cells-Derived Extracellular Vesicles Mediate the Transfer of IGF-I to the Liver and Ameliorate Hepatic Fibrogenesis in Mice

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

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The 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

Anti-Tumoral Activity of Single and Combined Regorafenib Treatments in Preclinical Models of Liver and Gastrointestinal Cancers

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

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Enanta Announces Positive Results of ARGON-1 Study of Its Lead FXR Agonist, EDP-305, for the Treatment of NASH

Enanta 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 Human-on-a-Chip Technology Awarded First Phase of $3.8 Million Milestone-Based NIH Grant to Study Opiate Overdoses in Collaboration with UCF

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

NIH 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

NEW Cancer Epigenetics: New Mechanisms and Therapeutic Opportunities
January 26-30, 2020
Keystone, Colorado, United States

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NEW 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)

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