Hepatic Cell News Volume 3.25 | Jul 12 2019

TOP STORY

A Human Liver Cell Atlas Reveals Heterogeneity and Epithelial Progenitors

Scientists performed single-cell RNA sequencing of about 10,000 cells from normal liver tissue from nine human donors to construct a human liver cell atlas. Their analysis identified previously unknown subtypes of endothelial cells, Kupffer cells, and hepatocytes, with transcriptome-wide zonation of some of these populations. [Nature] Abstract | Press Release | Editorial

(Ranked by impact factor of the journal)

PMPCB Silencing Sensitizes HCC Tumor Cells to Sorafenib Therapy

Silencing β-subunit mitochondrial-processing peptidase (PMPCB) increased hepatocellular carcinoma (HCC) tumor cell susceptibility to sorafenib therapy, decreased liver tumor burden, and improved survival of tumor-bearing mice receiving sorafenib. Moreover, sorafenib + PMPCB shRNA combination therapy led to attenuated liver tumor burden and improved survival outcome for tumor-bearing mice and reduced colony formation in murine and human HCC cell lines in vitro. [Mol Ther] Abstract

Mesenchymal Stem Cell-Mediated Delivery of an Oncolytic Adenovirus Enhances Antitumor Efficacy in Hepatocellular Carcinoma

The authors examined the feasibility of using human mesenchymal stem cells (MSCs) as a carrier to systemically deliver a hepatocellular carcinoma (HCC)-specific oncolytic adenovirus (HCC-oAd) in an HCC orthotopic tumor model. They showed that MSCs could be effectively infected by HCC-oAd through modification of the virus’ fiber domain and that the virus replicated efficiently in the cell carrier. [Cancer Res] Abstract

Eukaryotic Elongation Factor 2 Kinase Promotes Angiogenesis in Hepatocellular Carcinoma via PI3K/Akt and STAT3

Silencing of elongation factor 2 kinase (eEF2K) in endothelial cells (HUVECs) led to a reduction in vascularization, evidenced by a decrease in capillary-like structures in the matrigel. Notably, knocking down eEF2K reduced the expression of angiogenesis-related growth factors in highly metastatic liver cancer cells and the expression of growth factor receptors on HUVECs, and thus restricted signaling crosstalk that promotes angiogenesis between hepatocellular carcinoma cells and endothelial cells. [Int J Cancer] Abstract

EZH2, JMJD3, and UTX Epigenetically Regulate Hepatic Plasticity Inducing Retro-Differentiation and Proliferation of Liver Cells

Inhibition of JMJD3 and UTX H3K27 demethylase activity by GSK-J4 epi-drug reverted the phenotype of HepaRG DMSO-differentiated cells and human primary hepatocytes, drastically decreasing expression of hepatic markers and inducing cell proliferation. In parallel, inhibition of EZH2 dimethylation and trimethylation of H3K27 activity by GSK-126 epi-drug induced upregulation of hepatic markers and downregulated the expression of cell cycle inhibitor genes. [Cell Death Dis] Full Article

Drp1 and RB Interaction to Mediate Mitochondria-Dependent Necroptosis Induced by Cadmium in Hepatocytes

Cadmium (Cd)Cl₂ exposure induced necroptosis and hepatic injury both in vivo and in vitro. Moreover, Drp1 and RB protein were up-regulated and translocated to mitochondria in CdCl2-exposed hepatocytes. [Cell Death Dis] Full Article

Elevated N-Methyltransferase Expression Induced by Hepatic Stellate Cells Contributes to the Metastasis of Hepatocellular Carcinoma via Regulation of the CD44v3 Isoform

Investigators report that activated hepatic stem cells induced upregulation of nicotinamide N-methyltransferase (NNMT), which is known to regulate multiple metabolic pathways in hepatoma cells of the liver. High levels of NNMT in hepatacellular carcinoma tissues were positively correlated with vascular invasion, increased serum HBV-DNA levels and distant metastasis. [Mol Oncol] Abstract | Full Article

miR-26b-5p Helps in EpCAM⁺ Cancer Stem Cells Maintenance via HSC71/HSPA8 and Augments Malignant Features in HCC

iTRAQ based protein profiling and Next Generation Sequencing was performed on EpCAM⁺/EpCAM^– cells isolated from heptacellular carcinoma (HCC) and EpCAM⁺ cells from non-cancerous/non-cirrhotic control liver tissues. Validations were done using qRT-PCR, flow cytometry and western blotting followed by in vitro and in vivo functional studies. [Liver Int] Abstract

Fatty Acid Desaturase 2 Is Up-Regulated by the Treatment with Statin through Geranylgeranyl Pyrophosphate-Dependent Rho Kinase Pathway in HepG2 Cells

Researchers investigated the roles of the intrinsic mevalonate cascade and Rho-dependent pathway in long chain polyunsaturated fatty acid synthesis, especially focusing on fatty acid desaturases 2, using the human hepatocellular carcinoma cell line HepG2. Cell number and the activity of caspase-3 and 7 was measured using a commercial kit. [Sci Rep] Full Article

Upregulation of RUNX1 Suppresses Proliferation and Migration through Repressing VEGFA Expression in Hepatocellular Carcinoma

Scientists showed the suppressive role of runt-related transcription factor 1 (RUNX1) in the proliferation and migration of hepatocytes. In addition, the repressor RUNX1 functioned as a transcription factor on the promoter of vascular endothelial growth factor A (VEGFA) to inhibit the expression of VEGFA. [Pathol Oncol Res] Abstract

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Immune Checkpoint Inhibitors for Hepatocellular Carcinoma

A recent demonstration that immunotherapy is effective for patients with hepatocellular carcinoma (HCC) is a milestone in the history of this recalcitrant disease. The treatment of HCC has been a challenge, and for many years was limited to the tyrosine kinase inhibitor sorafenib and to several novel tyrosine kinase inhibitors that have shown efficacy and have been approved. [Cancer] Abstract

Current Understanding of Adipose-Derived Mesenchymal Stem Cell-Based Therapies in Liver Diseases

The authors comprehensively analyze landmark studies that address the isolation, proliferation, and hepatogenic differentiation of adipose-derived mesenchymal stem cells (ADMSCs) and summarize the therapeutic effects of ADMSCs in animal models of liver diseases. They also discuss key points related to improving the hepatic differentiation of ADMSCs via exposure of the cells to cytokines and growth factors, extracellular matrix, and various physical parameters in in vitro culture. [Stem Cell Res Ther] Full Article

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

Gilead Sciences and Renown Institute for Health Innovation Announce Strategic Collaboration to Advance Understanding of Nonalcoholic Steatohepatitis (NASH)

Gilead Sciences, Inc. announced a strategic collaboration to collect and analyze genetic and electronic health data that can enhance the understanding of NASH and potentially inform development of treatment options for the disease. [Gilead Sciences, Inc.] Press Release

Metacrine Doses First Patient in 12-Week NASH Proof-of-Concept Trial with a Sustained FXR Agonist

Metacrine, Inc. announced that the first patient has been dosed in its 12-week, Phase Ib trial of MET409, a potent, sustained, non-bile acid farnesoid x-receptor agonist small molecule, in patients with non-alcoholic steatohepatitis. [Metacrine, Inc.] Press Release

ADMA Biologics Receives FDA Approval for License Transfers for BIVIGAM^® and Nabi-HB^®

ADMA Biologics, Inc. announced that the FDA has notified ADMA the licenses for BIVIGAM^® and Nabi-HB^® have been revoked from Biotest Pharmaceuticals Corporation, US License No. 1792 and transferred and issued to ADMA’s US License No. 2019. [ADMA Biologics] Press Release

University of California Loses Access to New Journal Articles Published by Elsevier after Research Access Fight

Researchers in the University of California system lost subscription access to the major publisher Elsevier, the result of a closely watched fight between the two parties over how academic research should get read and paid for. [STAT News] Editorial

Sweden Passes Law For National Research Misconduct Agency

After several high-profile cases, the country’s government is creating a board to oversee and investigate all serious allegations of scientific misconduct. [The Scientist] Editorial

As Visa Difficulties Persist, Scientists Push for Change

Individual researchers and science societies are finding solutions so colleagues around the globe can attend conferences, from remote presentations to relocating conferences. [The Scientist] Editorial

NEW JSH International Liver Conference
October 1-2, 2019
Osaka, Japan

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

NEW Project Leader – Chronic Liver Disease Drug Discovery (Inserm Institute for Viral and Liver Disease)

Research Associate – System Level Analysis of Human Organogenesis (The University of Manchester)

Postdoctoral Position – Human Liver Microphysiology Systems (University of Pittsburgh Drug Discover Institute)

Research Professor – Nutrition & Metabolic Diseases (KU Leuven)

Research Lab Specialist – Tumor Microenvironment & Cell Behavior (University of Southern California)

PhD Position – Cytokine-Induced Metabolic Rewiring of the Liver (Research Center for Molecular Medicine of the Austrian Academy of Sciences)

Postdoctoral Scientist – Epigenetic Mechanisms of NAFLD (Institute of Hepatology, Foundation for Liver Research)

Postdoctoral Position – Liver Disease (University of Illinois at Chicago)

Research Assistant – Liver Immunology (Maynooth University)

Faculty Position/Director – Cancer Research (Lewis Katz School of Medicine at Temple University)

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