Hepatic Cell News Volume 2.01 | Jan 12 2018

TOP STORY

Diverse Modes of Clonal Evolution in HBV-Related Hepatocellular Carcinoma Revealed by Single-Cell Genome Sequencing

Using single-cell whole-genome sequencing to profile 96 tumor cells and 15 normal liver cells, collected from three male patients with hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC), scientists confirmed that copy number variations occur early in hepatocarcinogenesis but thereafter remain relatively stable throughout tumor progression. [Cell Res] Full Article

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Disruption of Adenosine 2A Receptor Exacerbates NAFLD through Increasing Inflammatory Responses and SREBP1c Activity

Researchers demonstrated that disruption of adenosine 2A receptor in both macrophage and hepatocytes accounts for increased severity of non-alcoholic fatty liver disease (NAFLD), likely through increasing inflammation and through elevating lipogenic events due to stimulation of sterol regulatory element-binding protein 1c (SREBP1c) expression and transcription activity. [Hepatology] Abstract

Single Cell Analysis Reveals Cancer Stem Cell Heterogeneity in Hepatocellular Carcinoma

Investigators combined transcriptomic and functional analyses of hepatocellular carcinoma cells at the single cell level to assess the degree of cancer stem cells (CSC) heterogeneity. They provided evidence that hepatic CSCs at the single-cell level are phenotypically, functionally and transcriptionally heterogeneous. [Hepatology] Abstract

Depletion of S100A4⁺ Stromal Cells Stromal Cells Does Not Prevent HCC Development but Reduces the Stem Cell-Like Phenotype of the Tumors

The authors generated a new mouse model allowing for the depletion of S100A4⁺ cells in a mouse model of hepatocellular carcinoma (HCC) with stemness properties, by crossing mice with hepatic deletion of phosphatase and tensin homolog with mice expressing viral thymidine kinase under the control of S100A4 promoter. Depletion of S100A4⁺ cells by ganciclovir injection did not prevent the development of HCC but reduced the stemness phenotype of the tumor as measured by the expression of progenitor cell, biliary cell and hepatocyte markers. [Exp Mol Med] Full Article

Perilipin 5 and Liver Fatty Acid Binding Protein Function to Restore Quiescence in Mouse Hepatic Stellate Cells

Scientists indicated that liver fatty acid-binding protein is required for perilipin 5 to activate a transcriptional program that restores lipid droplet formation and reverses hepatic stellate cell activation. [J Lipid Res] Abstract | Full Article

DEPDC5 Deficiency Contributes to Resistance to Leucine Starvation via p62 Accumulation in Hepatocellular Carcinoma

Researchers established hepatocellular carcinoma (HCC) cells knocked out for DEPDC5 by using the CRISPR/Cas9 system, and elucidated that cell viability of the DEPDC5 knockout cells was higher than that of the DEPDC5 wild-type under leucine starvation. [Sci Rep] Full Article

Development of a Recombinant Murine Tumor Model Using Hepatoma Cells Expressing Hepatitis C Virus (HCV) Non-Structural Antigens

Investigators tested the therapeutic potential of recombinant anti-HCV-specific vaccines based on two fundamentally different attenuated pathogen vaccine systems – attenuated Salmonella and recombinant adenoviral vector based vaccine. While attenuated Salmonella that secreted HCV antigens limited growth of the HCV-recombinant tumors when used in a therapeutic vaccination trial, replication-competent but non-infectious adenovirus expressing non-structural HCV antigens showed overall greater survival and reduced weight loss compared to non-replicating non-disseminating adenovirus. [J Viral Hepat] Abstract

Long Noncoding RNA CASC2 Regulates Hepatocellular Carcinoma Cell Oncogenesis through miR-362-5p/Nf-κB Axis

The authors demonstrated that cancer susceptibility candidate 2 (CASC2) is downregulated in human hepatocellular carcinoma (HCC) tissues and HCC cell lines as compared to adjacent non-tumor tissues and a liver cell line, respectively. After finding that CASC2 knockdown significantly promotes HCC cells migration and invasion as well as that CASC2 overexpression inhibits cell migration and invasion, they identified the microRNA miR-362-5p as an endogenous target of CASC2. [J Cell Physiol] Abstract

The Bioactive Extract of Pinnigorgia sp. Induces Apoptosis of Hepatic Stellate Cells via ROS-ERK/JNK-Caspase-3 Signaling

Researchers identified that the extract from a gorgonian coral Pinnigorgia sp. (Pin) induced apoptosis of hepatic stellate cell (HSC)-T6 cells. Pin inhibited the viability of HSC-T6 cells and increased their subG1 population, DNA fragmentation, caspase-3 activation, and reactive oxygen species production in a concentration-dependent manner. [Mar Drugs] Full Article

Vitamin C Preferentially Kills Cancer Stem Cells in Hepatocellular Carcinoma via SVCT-2

Panels of human hepatocellular carcinoma (HCC) cell lines as well as HCC patient-derived xenograft models were employed to investigate the anti-tumor effects of pharmacologic Vitamin C (L-ascorbic acid, ascorbate, VC). In vitro and in vivo experiments further demonstrated that clinically achievable concentrations of VC induced cell death in liver cancer cells and the response to VC was correlated with sodium-dependent vitamin C transporter 2 (SVCT-2) expressions. [npj Precis Oncol] Full Article

Non-Coding RNAs in Hepatocellular Carcinoma: Molecular Functions and Pathological Implications

The authors summarize the common deregulation of small and long non-coding RNAs (ncRNAs) in human hepatocellular carcinoma (HCC). They also comprehensively review the pathological roles of ncRNAs in liver carcinogenesis, epithelial-to-mesenchymal transition and HCC metastasis and discuss the potential applications of ncRNAs as diagnostic tools and therapeutic targets in human HCC. [Nat Rev Gastroenterol Hepatol] Abstract

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STEMCELL Technologies Brings Groundbreaking Intestinal and Brain Organoid Culture Tools to the Global Research Community

STEMCELL Technologies Inc. has released two product lines for organoid research that will enable scientists to create powerful models for studying human disease in the lab. [STEMCELL Technologies Inc.] Press Release

TARGET Pharmasolutions to Advance NASH Research through New Collaboration

TARGET PharmaSolutions, Inc. is pleased to announce that Novartis has entered into a long-term strategic alliance for TARGET-NASH. [TARGET PharmaSolutions, Inc.] Press Release

Successful Completion of Pre-Clinical Safety Studies with MIV-818, Enabling Start of Phase I Clinical Studies in 2018

MIV-818 is Medivir’s proprietary liver-targeted nucleotide prodrug for the treatment of hepatocellular carcinoma and other forms of liver cancer. It is the first development project to emerge from Medivir’s in-house drug discovery efforts in oncology. [Medivir AB] Press Release

Rising Star Appointed UK Science Minister

The United Kingdom has gained a new science minister as part of a broader reshuffle of government posts. Sam Gyimah, who moves from the Ministry of Justice, was appointed minister for universities and science, replacing Jo Johnson. [Nature News] Editorial

Faced with Public Pressure, Research Institutions Step Up Reporting of Clinical Trial Results

The reporting of clinical trial results to a public database — mandated by a ten-year-old federal law — has improved sharply in the last two years, with universities and other nonprofit research centers leading the way. [STAT News] Editorial

NEW Applications of Organoid Technology
May 27-June 2, 2018
Bar Harbor, Maine, United States

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NEW Postdoctoral Position – Feeding Regulated Chromatin Organization and Gene Transcription in the Liver (University of Southern Denmark)

NEW Postdoctoral Position – Liver Diseases (University of Illinois)

NEW Part-Time Postdoctoral Scientist – HCV Vaccine Model Development (University of Oxford)

Postdoctoral Research Fellow – Liver Cancer Pathogenesis and Immunobiology (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Liver Cancer (University Health Network)

Postdoctoral Scholar Position – Cancer & Stem Cell Epigenomics (University of California, Davis)

Postdoctoral Fellow – Liver Tissue Engineering (Massachusetts General Hospital and Harvard Medical School)

Assistant, Associate or Full Professor – Hepatology (University of California, San Diego)

Research Fellow – Hepatitis B Virology (National University of Singapore)

Research Scientist – Chronic Fibrotic and Metabolic Diseases (Gilead Sciences Inc.)

Faculty Positions – Liver Health and Disease (University of Pittsburgh)

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