Hepatic Cell News Volume 4.02 | Jan 24 2020

TOP STORY

Identification of Lineage-Specific Transcription Factors That Prevent Activation of Hepatic Stellate Cells and Promote Fibrosis Resolution

Human hepatic stellate cells (HSCs) were isolated from livers denied for transplantation. Scientists compared changes in gene expression patterns and epigenetic modifications in primary mouse and human HSCs. Transcription factors were knocked down with small hairpin RNAs in mouse HSCs. [Gastroenterology] Abstract | Press Release

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Hepatitis Delta Virus Histone Mimicry Drives the Recruitment of Chromatin Remodelers for Viral RNA Replication

Researchers showed that S-HDAg bound the bromodomain (BRD) adjacent to zinc finger domain 2B (BAZ2B) protein, a regulatory subunit of BAZ2B-associated remodeling factor ISWI chromatin remodeling complexes. shRNA-mediated silencing of BAZ2B or its inactivation with the BAZ2B BRD inhibitor GSK2801 impaired HDV replication in HDV-infected human hepatocytes. [Nat Commun] Full Article

Cooperation Between MYC and β-Catenin in Liver Tumorigenesis Requires Yap/Taz

Activation of WNT/β-catenin signaling strongly accelerated MYC-driven carcinogenesis in the liver. Both pathways also cooperated in promoting cellular transformation in vitro, demonstrating their cell-autonomous action. [Hepatology] Abstract

Hepatic Neddylation Targets and Stabilizes Electron Transfer Flavoproteins to Facilitate Fatty Acid β-Oxidation

Neddylation inhibition by various strategies resulted in decreased protein levels of electron transfer flavoproteins (ETF) in neonatal livers and embryonic hepatocytes. Hepatic neddylation also enhanced ETF expression in adult mice and prevented fasting-induced steatosis and mortality. Neddylation was active in hepatic mitochondria. [Proc Natl Acad Sci USA] Abstract

E2F-Family Members Engage the PIDDosome to Limit Hepatocyte Ploidy in Liver Development and Regeneration

The authors showed that the PIDDosome, a signaling platform essential for caspase-2-activation, limited hepatocyte ploidy and was instructed by the E2F network to control p53 in the developing as well as regenerating liver. Casp2 and Pidd1 acted as direct transcriptional targets of E2F1 and its antagonists, E2F7 and E2F8, that together co-regulated PIDDosome expression during juvenile liver growth and regeneration. [Dev Cell] Abstract

LINC00662 Promotes Hepatocellular Carcinoma Progression via Altering Genomic Methylation Profiles

The authors demonstrated that the lncRNA LINC00662 was correlated with survival and exhibited oncogenic properties, both in vitro and in vivo. Moreover, they determined that LINC00662 could lead to genome-wide hypomethylation and altered the genomic methylation profile by synchronously reducing the S-adenosylmethionine level and enhancing the S-adenosylhomocysteine level. [Cell Death Differ] Abstract

The Nuclear Translocation of Transketolase Inhibits the Farnesoid Receptor Expression by Promoting the Binding of HDAC3 to FXR Promoter in Hepatocellular Carcinoma Cell Lines

Investigators found that transketolase (TKT) deficiency protected the liver from DNA damage by increasing levels of ribose 5-phosphate and nucleotides. They found TKT deficiency reduced bile acids and loss of TKT promoted the farnesoid receptor expression. [Cell Death Dis] Full Article

Validation of miR-20a as a Tumor Suppressor Gene in Hepatocellular Carcinoma Using Hepatocyte-Specific Hyperactive piggyBac Transposons

Scientists developed a more aggressive hepatocellular carcinoma (HCC) model by overexpression of HRASG12V and c-MYC oncogenes that accelerated HCC development after only six weeks. The tumor suppressor effect of miR-20a could be demonstrated even in this rapid-onset HRASG12V/c-MYC HCC model consistent with significantly prolonged survival and decreased HCC tumor burden. [Mol Ther Nucleic Acids] Abstract | Full Article

Human Liver Stem Cells Express UGT1A1 and Improve Phenotype of Immunocompromised Crigler Najjar Syndrome Type I Mice

To assess whether human liver stem cells (HLSCs) expressed UGT1A1, de-cellularized mouse liver scaffolds were repopulated with these cells. After 15 days’ culture ex vivo, HLSCs differentiated into hepatocyte-like cells showing UGT1A1 expression and activity. [Sci Rep] Full Article

Cell Release During Perfusion Reflects Cold Ischemic Injury in Rat Livers

Researchers showed that hepatocytes, sinusoidal endothelial, stellate, and liver-specific immune cells were released into perfusates from Lewis rat livers as a result of cold ischemia and machine perfusion. Perfusate comparison analysis of fresh livers and cold ischemic livers showed that the released cell profiles were significantly altered by the duration of cold ischemia. [Sci Rep] Full Article

SEMA3F Promotes Liver Hepatocellular Carcinoma Metastasis by Activating Focal Adhesion Pathway

Investigators demonstrated that semaphorin-3F (SEMA3F) was significantly upregulated in LIHC tissues, compared with normal controls. Moreover, the expression value of SEMA3F was positively correlated with patients’ pathological stages and tumor metastasis, predicting a poor overall survival. [DNA Cell Biol] Abstract

Enhanced Glucose Metabolism Mediated by CD147 Contributes to Immunosuppression in Hepatocellular Carcinoma

Several hepatocellular carcinoma (HCC) cell lines and corresponding nude mice xenografts models differing in CD147 expressions were established to directly investigate the role of CD147 in the reprogramming of glucose metabolism, and to determine the underlying molecular mechanisms. Immunohistochemistry analyses and flow cytometry were used to identify the relationship between reprogrammed glycolysis and immunosuppression in HCC. [Am J Med Genet A] Abstract

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Targeting FGF21 for the Treatment of Nonalcoholic Steatohepatitis

Fibroblast growth factor 21 (FGF21) and its analogs have emerged as a potential new therapeutic strategy for the treatment of nonalcoholic steatohepatitis (NASH). In fact, FGF21 deficiency favors the development of steatosis, inflammation, hepatocyte damage, and fibrosis in the liver, whereas administration of FGF21 analogs ameliorates NASH by attenuating these processes. [Trends Pharmacol Sci] Abstract

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AXIM^® Biotechnologies Acquiree Sapphire Biotech, Inc. Signs License Agreement to Exclusively License Patent Rights in Cancer Technology

AXIM^® Biotechnologies, Inc. announced that its acquiree Sapphire Biotech, Inc. has signed an agreement with Skysong Innovations, LLC to exclusively license rights to pharmaceutical compositions and methods for the treatment of cancer. [AXIM^® Biotechnologies, Inc.] Press Release

Exelixis Announces Results for Combination of Cabozantinib and Nivolumab with or without Ipilimumab in Advanced Hepatocellular Carcinoma

Exelixis, Inc. announced Phase I/II clinical trial results from the combination of cabozantinib and nivolumab with or without ipilimumab in advanced hepatocellular carcinoma (HCC). CheckMate 040 is a Phase I/II study that includes an exploratory cohort of patients with advanced HCC who were either treatment naïve or who were intolerant to or had progressed on prior sorafenib therapy. [Exelixis, Inc.] Press Release

‘We Need a People’s Cryo-EM’ Scientists Hope to Bring Revolutionary Microscope to the Masses

X-ray crystallography has dominated structural biology ever since, but it has an Achilles’ heel: Some proteins just can’t be coaxed to form crystals, which scatter x-rays to reveal structure. Cryo–electron microscopy dodges the problem of crystallization with a flash-freezing process that fixes proteins in thin films of glassy ice. [ScienceInsider] Editorial

Campus Attacks by Nationalists and Police Alarm India’s Scientific Community

The attack on one of India’s most prestigious universities sent shock waves around the country and is the latest sign that the political forces tearing apart Indian society are also affecting the country’s academic community. Students at JNU, a liberal bastion, had been on strike for months against both a major hike in student fees and the government’s controversial Citizenship Amendment Act, widely decried as discriminatory against Muslims. [ScienceInsider] Editorial

NEW International Society for Stem Cell Research (ISSCR)
June 24-27, 2020
Boston, Massachusetts, United States

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

NEW Postdoctoral Position – Culturing ‘Foie Gras’ (KU Leuven)

NEW Team Leader – Cholangiocytes (Miromatrix Medical)

Postdoctoral Fellow – Cell Therapy for Liver Repair (University of Edinburgh)

Program Leader – Propionic Acidemia Research (None)

Postdoctoral Fellow – Metabolic Dysfunction (Lewis Katz School of Medicine)

Postdoctoral Researchers – MicroRNAs in NAFLD (Weill Cornell Medicine)

Postdoctoral Fellow – Translational Cancer Research (University of New Mexico Comprehensive Cancer Center)

Research Associate – Liver Damage (University of Colorado Denver)

Postdoctoral Researcher – Cell Biology of the Liver (Max Planck Institute of Immunobiology and Epigenetics)

Postdoctoral Fellow – Liver Pathology (University of Illinois at Chicago)

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