Hepatic Cell News Volume 4.06 | Feb 21 2020

TOP STORY

Cell-Type-Specific Signaling Networks in Heterocellular Organoids

Researchers report multivariate single-cell analysis of networks in organoids and organoid co-cultures. Simultaneous analysis by mass cytometry of 28 PTMs in >1 million single cells derived from small intestinal organoids revealed cell-type- and cell-state-specific signaling networks in stem, Paneth, enteroendocrine, tuft and goblet cells, as well as enterocytes. [Nat Methods] Abstract | Press Release

(Ranked by impact factor of the journal)

Targeting Hepatic Glutaminase 1 Ameliorates Non-Alcoholic Steatohepatitis by Restoring Very-Low-Density Lipoprotein Triglyceride Assembly

The authors showed that the hepatic high-activity glutaminase 1 isoform (GLS1) was overexpressed in non-alcoholic steatohepatitis (NASH). Importantly, GLS1 inhibition reduced lipid content in choline and/or methionine deprivation-induced steatotic mouse primary hepatocytes, in human hepatocyte cell lines, and in NASH mouse livers. [Cell Metab] Abstract | Graphical Abstract

Chromatin Remodeling Factor ARID2 Suppresses Hepatocellular Carcinoma Metastasis via DNMT1-Snail Axis

Investigators found that ARID2 expression was significantly decreased in metastatic hepatocellular carcinoma (HCC) tissues, showing negative correlation with pathological grade, organ metastasis and positive association with survival of HCC patients. ARID2 inhibited migration and invasion of HCC cells in vitro and metastasis in vivo. [Proc Natl Acad Sci USA] Abstract

OTULIN Prevents Liver Inflammation and Hepatocellular Carcinoma by Inhibiting FADD- and RIPK1 Kinase-Mediated Hepatocyte Apoptosis

The authors showed that ablation of OTULIN in liver parenchymal cells in mice caused severe liver disease which was characterized by liver inflammation, hepatocyte apoptosis, and compensatory hepatocyte proliferation, leading to steatohepatitis, fibrosis, and hepatocellular carcinoma. [Cell Rep] Full Article | Graphical Abstract

DNA and RNA Sequencing Identified a Novel Oncogene VPS35 in Liver Hepatocellular Carcinoma

Scientists showed that a component of the retromer complex-the vacuolar protein sorting-associated protein 35 (VPS35)-promoted the proliferation of hepatoma cell through the PI3K/AKT signaling pathway. In VPS35-knockout hepatoma cells, a significantly reduced distribution of membrane fibroblast growth factor receptor 3 demonstrated the effects of VPS35 on sorting and trafficking of transmembrane receptor. [Oncogene] Abstract

CHD4/NuRD Complex Regulates Complement Gene Expression and Correlates with CD8 T Cell Infiltration in Human Hepatocellular Carcinoma

Researchers analyzed the expression of the Nucleosome Remodeling and Deacetylation (NuRD) complex in hepatocellular carcinoma (HCC) and evaluated the prognostic value of NuRD complex expression in HCC using the RNA-seq data obtained from the TCGA project. They examined the effect of CHD4 knockdown on HCC cell proliferation, apoptosis, migration, invasion, epithelial-mesenchymal transition, colony-forming ability, and on complement gene expression. [Clin Epigenetics] Abstract

Silencing lncRNA Lfar1 Alleviates the Classical Activation and Pyroptosis of Macrophage in Hepatic Fibrosis

The authors demonstrated that the liver-enriched lncRNA Lfar1, which has been reported to promote hepatic fibrosis through inducing hepatic stellate cell activation and hepatocyte apoptosis, was dysregulated during proinflammatory M1 activation and pyroptosis of macrophage. [Cell Death Dis] Full Article

Exosomal miR-103-3p from LPS-Activated THP-1 Macrophage Contributes to the Activation of Hepatic Stellate Cells

Scientists investigated the role of exosomes between THP-1 macrophages and hepatic stellate cells (HSCs) in the progression of liver fibrosis. Exosomes originating from lipopolysaccharide (LPS)-treated THP-1 macrophages promoted HSC proliferation and induced the increased expression of fibrotic genes. [FASEB J] Full Article

CCN1 Promotes Hepatic Steatosis and Inflammation in Non-Alcoholic Steatohepatitis

CCN1 up-regulation was found to be closely related with steatosis in patients with non-alcoholic steatohepatitis (NASH), obese mice and an FFA-treated hepatocyte model. Controlling the expression of CCN1 in murine NASH models demonstrated that CCN1 increased the severity of steatosis and inflammation. [Sci Rep] Full Article

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Advances in Non-Invasive Assessment of Hepatic Fibrosis

Non-invasive tests are valuable for excluding advanced fibrosis or cirrhosis; however, they are not sufficiently predictive when used in isolation. Combining serum and elastography techniques increases diagnostic accuracy and can be used as screening and confirmatory tests, respectively. [Gut] Abstract

Synthetic Lethality: A Promising Therapeutic Strategy for Hepatocellular Carcinoma

The authors introduce the concept of synthetic lethality, the screening used to study synthetic lethality, and the identified and potential genetic interactions that induce synthetic lethality in hepatocellular carcinoma (HCC). In addition, they propose opportunities and challenges for translating synthetic lethal interactions to the clinical treatment of HCC. [Cancer Lett] Full Article

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Cyclo Therapeutics Announces Completion of Enrollment in Its Phase I/II Trial to Evaluate Trappsol^® Cyclo™ for the Treatment of Niemann-Pick Disease Type C

Cyclo Therapeutics, Inc. announced that it has completed patient enrollment in its Phase I/II trial to evaluate the safety, tolerability, and efficacy of Trappsol^® Cycle™ administered intravenously to Niemann-Pick Disease Type C1 patients. [Cyclo Therapeutics, Inc.] Press Release

MD Anderson Receives More Than $20 Million in CPRIT Funding

The University of Texas MD Anderson Cancer Center was awarded more than $20 million from the Cancer Prevention and Research Institute of Texas (CPRIT) to support research, clinical translation, prevention and recruitment efforts. In total, MD Anderson received 28% of the $78 million in awards announced by CPRIT. [MD Anderson Cancer Center] Press Release

Has the UK Science Minister Been Demoted?

A government reshuffle in the United Kingdom has born another new science minister – a position that has seen a revolving door of appointees, firings and resignations in recent years. The latest appointment also comes with an apparent political demotion for the role, which expert observers say is in conflict with a government that appears to have put research and innovation at the heart of its agenda. [Nature News] Editorial

NIH Hosts Nonhuman Primate Workshop Amidst Increased Scrutiny of Monkey Research

More than three years after it hosted a workshop on the science and ethics of biomedical studies on monkeys, the National Institutes of Health (NIH) this week convened another workshop on nonhuman primate research. And much like the previous event, the meeting is drawing sharply divergent reactions from biomedical and animal advocacy groups. [ScienceInsider] Editorial

Animal Welfare Records Return to USDA Website

On February 18, the US Department of Agriculture replaced on its website the animal welfare records that the agency had removed in early 2017 and added records that had been generated since, as ordered by Congress, The Washington Post reports. These documents, unredacted and searchable, include thousands of reports from unannounced inspections at research labs as well as zoos, circuses, dog breeders, and other facilities. [The Scientist] Editorial

White House Formally Invites Public Comment on Open-Access Policies

The White House issued a notice seeking comment on its effort to enhance public access to federally funded research. It’s an old idea creating new controversy. White House Office of Science and Technology Policy (OSTP) Director Kelvin Droegemeier is pushing back against publishers that in December said the administration was quietly pursuing an executive order to require immediate free distribution of taxpayer funded research. [ScienceInsider] Editorial

NEW Tumor Heterogeneity: From Single Cells to Clinical Impact
September 10-13, 2020
Philadelphia, Pennsylvania, United States

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NEW 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)

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

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

Team Leader – Cholangiocytes (Miromatrix Medical)

Program Leader – Propionic Acidemia Research (Cambridge, Massachusetts)

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)

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