Hepatic Cell News Volume 4.08 | Mar 6 2020

TOP STORY

Fast and Efficient Generation of Knock-In Human Organoids Using Homology-Independent CRISPR-Cas9 Precision Genome Editing

A double reporter-in which the mitotic spindle was labeled by endogenously tagged tubulin and the cell membrane by endogenously tagged E-cadherin-uncovered modes of human hepatocyte division. Combining tubulin tagging with TP53 knock-out revealed that TP53 was involved in controlling hepatocyte ploidy and mitotic spindle fidelity. [Nat Cell Biol] Abstract

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Complement C1q Mediates the Expansion of Periportal Hepatic Progenitor Cells in Senescence-Associated Inflammatory Liver

Senescent β-catenin-depleted hepatocytes in aged mice created an inflammatory microenvironment that stimulated periportal hepatic progenitor cell expansion but arrested differentiation, which predisposed mice to the development of liver tumors. [Proc Natl Acad Sci USA] Abstract

Long Noncoding RNA LINC00324 Exerts Protumorigenic Effects on Liver Cancer Stem Cells by Upregulating Fas Ligand via PU Box Binding Protein

The effect of LINC00324 on viability, proliferation, migration, invasion, and apoptosis as well as the tumorigenesis of transfected cells was examined with gain- and loss-of-function experiments. LINC00324 and Fas ligan were highly expressed in hepatocellular carcinoma. [FASEB J] Full Article

GR-Mediated FTO Transactivation Induces Lipid Accumulation in Hepatocytes via Demethylation of m⁶A on Lipogenic mRNAs

The authors used both in vivo and in vitro models of glucocorticoid-induced hepatic lipid accumulation and demonstrated that the activation of lipogenic genes and accumulation of lipid in liver cells were mediated by glucocorticoid receptor (GR)-dependent FTO transactivation and N6-methyladenosine (m⁶A) demethylation on mRNA of lipogenic genes. [RNA Biol] Abstract | Graphical Abstract

Heat Shock Protein 12A Is a Novel PCNA-Binding Protein and Promotes Hepatocellular Carcinoma Growth

Gain- and loss-of-functional studies demonstrated that the proliferation of hepatocellular carcinoma HepG2 cells, as well as β-catenin expression and nuclear translocation, were promoted by HSPA12A overexpression, but in turn suppressed by HSPA12A knockdown. [FEBS J] Abstract

Odontogenic Infection by Porphyromonas gingivalis Exacerbates Fibrosis in NASH via Hepatic Stellate Cell Activation

Galectin-3 produced from hepatic stellate cells (HSC) with Porphyromonas gingivalis (P.g.) infection and P.g.-derived LPS/lipoprotein stimulation stabilized TGFβ-receptor II resulting in increasing sensitivity for TGF-β1, finally leading to HSC differentiation via activating Smad and ERK signaling. [Sci Rep] Full Article

Hepatic Transporter Alterations by Nuclear Receptor Agonist T0901317 in Sandwich-Cultured Human Hepatocytes: Proteomic Analysis and PBPK Modeling to Evaluate Drug-Drug Interaction Risk

Researchers examined alterations in transporter protein levels in sandwich-cultured human hepatocytes measured by liquid chromatography-tandem mass spectrometry-based proteomic analysis after treatment with T0901317, the first described synthetic liver X receptor agonist. [J Pharmacol Exp Ther] Abstract

Aquaporin 8 Is Involved in H₂O₂-Mediated Differential Regulation of Metabolic Signaling by α1- and β-Adrenoceptors in Hepatocytes

Scientists investigated the reported opposite effects of hydrogen peroxide (H₂O₂) on metabolic signaling mediated by activated α1- and β-adrenoceptors in hepatocytes. In isolated rat hepatocytes, stimulation of α1-AR increased H₂O₂ production via NADPH oxidase 2 activation. [FEBS Lett] Abstract

TMT-Based Proteomics Analysis of the Anti-Hepatocellular Carcinoma Effect of Combined Dihydroartemisinin and Sorafenib

Investigators confirmed the significantly enhanced anti−hepatocellular carcinoma efficacy of dihydroartemisinin (DHA) in combination with sorafenib compared with that of each agent alone. Tandem Mass Tag (TMT) peptide labeling coupled with LC-MS/MS was used to quantify the proteins from the control, DHA, sorafenib, and DHA + sorafenib groups. [Biomed Pharmacother] Abstract

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One-Carbon Metabolism in Fatty Liver Disease and Fibrosis: One-Carbon to Rule Them All

The authors examine what scientists have learned about hepatic lipid metabolism and liver damage from the study of one-carbon metabolism thus far and highlights unexplored opportunities for future research. [J Nutr] Abstract

The Role of Sphingolipid Pathway in Liver Fibrosis: An Emerging New Potential Target for Novel Therapies

Investigators provide an overview on the role of sphingolipids (SLs) in liver pathobiology and focus on their potential role in the development of hepatic fibrosis. They describe recent evidence and suggest SLs are a promising potential therapeutic target for the treatment of liver disease and fibrosis. [Am J Physiol Cell Physiol] Abstract

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Arrowhead Pharmaceuticals Initiates Phase I/II Study of ARO-HSD in Normal Healthy Volunteers and Patients with NASH or Suspected NASH

Arrowhead Pharmaceuticals Inc. announced that it has dosed the first patients in AROHSD1001, a Phase I/II clinical study of ARO-HSD, the company’s investigational RNA interference therapeutic being developed as a treatment for patients. [Arrowhead Pharmaceuticals Inc.] Press Release

Arch Biopartners Expands Dosing in Phase I Trial for Metablok to Increase Dose Range for Future Phase II Studies

Arch Biopartners Inc. announced that it is expanding the dose range of Metablok for future Phase II trials targeting inflammation in the lung, the kidney and/or the liver by adding a cohort of eight healthy volunteers to receive the highest daily dose tested to date for three consecutive days. [Arch Biopartners Inc.] Press Release

MiNA Therapeutics Announces Initiation of Phase I Clinical Study of MTL-CEBPA in Combination with Anti-PD1 Checkpoint Inhibitor in Patients with Advanced Solid Tumours

MiNA Therapeutics announced the initiation and first patient treated in TIMEPOINT, a global Phase I/Ib clinical study of MTL-CEBPA in combination with anti-PD1 checkpoint inhibitor pembrolizumab in patients with advanced solid tumors. The study is designed to assess the safety, tolerability, pharmacology and clinical activity of MTL-CEBPA in combination with pembrolizumab in these patients. [MiNA Therapeutics] Press Release

Enanta’s HCV Collaboration Partner AbbVie Receives Marketing Authorization from European Commission to Shorten MAVIRET^® (Glecaprevir/Pibrentasvir) Duration to Eight Weeks for Treatment-Naïve Genotype 3 HCV Patients with Compensated Cirrhosis

Enanta Pharmaceuticals, Inc. announced that the European Commission has granted marketing authorization to its HCV collaboration partner AbbVie for MAVIRET^® to shorten the once-daily treatment duration from 12 to 8 weeks in treatment-naïve, compensated cirrhotic, chronic HCV patients with genotype 3 infection. [Enanta Pharmaceuticals, Inc.] Press Release

Trump Administration Expands Reach of EPA Secret Science Proposal

The US Environmental Protection Agency (EPA) evening released a controversial proposal to limit the scientific research used in the federal rule-making process. The draft “Strengthening Transparency in Regulatory Science” is part of the agency’s persistent effort to rework the foundation on which public health and environmental rules are crafted. [ScienceInsider] Editorial

China Bans Cash Rewards for Publishing Papers

Chinese institutions have been told to stop paying researchers bonuses for publishing in journals, as part of a new national policy to cut perverse incentives that encourage scientists to publish lots of papers rather than focus on high-impact work. [Nature News] Editorial

NEW International Society for Stem Cell Research (ISSCR): Advances in Stem Cell Research: From Single Cells to Organs
October 12-14, 2020
Paris, France

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

NEW Postdoctoral Fellow – The Microbiome in Liver Disease (University of Oslo)

NEW Postdoctoral Researcher – Liver Pathogenesis (Washington University in St. Louis)

NEW Program Leader – Methylmalonic Acidemia and Rare Diseases (Moderna)

Senior Postdoctoral Research Assistant – Liver Research (University of Dundee)

Postdoctoral Researchers – Diabetes, Liver, and Renal Disease (University of Oxford)

Network Manager – Non-Alcoholic Liver Disease (Hans-Knöll-Institute)

Postdoctoral Fellow – Fatty Liver Dieases (University of Kansas Medical Center)

Team Leader – Cholangiocytes (Miromatrix Medical)

Postdoctoral Fellow – Diabetes and Fatty Liver Disease (NIH National Heart, Lung, and Blood Institute)

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

Postdoctoral Researchers – MicroRNAs in NAFLD (Weill Cornell Medicine)

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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