Hepatic Cell News Volume 3.48 | Dec 20 2019

TOP STORY

AXIN2⁺ Pericentral Hepatocytes Have Limited Contributions to Liver Homeostasis and Regeneration

Using AXIN2 lineage tracing in BAC-transgenic mice, investigators confirmed the regenerative potential of intestinal stem cells but found limited roles for pericentral hepatocytes in liver parenchyma homeostasis. [Cell Stem Cell] Abstract | Graphical Abstract

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Broad Distribution of Hepatocyte Proliferation in Liver Homeostasis and Regeneration

Researchers found that modest proliferation of hepatocytes distributed throughout the lobule maintained hepatocyte mass and that most hepatocytes proliferated to regenerate it, with diploidy providing a growth advantage over polyploidy. [Cell Stem Cell] Abstract | Graphical Abstract

In Vivo Lineage Tracing of Polyploid Hepatocytes Reveals Extensive Proliferation during Liver Regeneration

Scientists developed a multicolor reporter allele system to genetically label and trace polyploid cells in situ. Multicolored polyploid hepatocytes underwent ploidy reduction and subsequent re-polyploidization after transplantation, providing direct evidence of the hepatocyte ploidy conveyor model. [Cell Stem Cell] Abstract | Graphical Abstract

LATS1 but Not LATS2 Represses Autophagy by a Kinase-Independent Scaffold Function

The authors report a pro-survival role of LATS1 but not LATS2 in hepatocellular carcinoma (HCC) cells. Specifically, LATS1 restricted lethal autophagy in HCC cells induced by sorafenib, the standard of care for advanced HCC patients. [Nat Commun] Full Article

PSPC1-Interchanged Interactions with PTK6 and β-Catenin Synergize Oncogenic Subcellular Translocations and Tumor Progression

Paraspeckle component 1 (PSPC1) upregulation or PSPC1-Y523F mutation promoted epithelial-mesenchymal transition, stemness, and metastasis via cytoplasmic translocation of active PTK6 and nuclear translocation of β-catenin, which interacted with PSPC1 to augment Wnt3a autocrine signaling. [Nat Commun] Full Article

A Tumorigenic Index for Quantitative Analysis of Liver Cancer Initiation and Progression

To probe the common mechanism of hepatocarcinogenesis, scientists interrogated temporal gene expression profiles in a group of mouse models with hepatic steatosis, fibrosis, inflammation, and, consequently, tumorigenesis. [Proc Natl Acad Sci USA] Abstract

Low-Level Saturated Fatty Acid Palmitate Benefits Liver Cells by Boosting Mitochondrial Metabolism via CDK1-SIRT3-CPT2 Cascade

Researchers demonstrated that although high-level palmitate (HPA) indeed induced lipotoxic effects in liver cells, low-level PA increased mitochondrial functions and alleviated the injuries induced by HPA or hepatoxic agent carbon tetrachloride. [Dev Cell] Abstract | Graphical Abstract

SIRT6 Promotes Hepatic Beta-Oxidation via Activation of PPARα

SIRT6 mediated PPARα inhibition of SREBP-dependent cholesterol and triglyceride synthesis. Mechanistically, SIRT6 bound PPARα coactivator NCOA2 and decreased liver NCOA2 K780 acetylation, which stimulated its activation of PPARα in a SIRT6-dependent manner. [Cell Rep] Full Article | Graphical Abstract

Inhibition of TRPM7 Blocks MRTF/SRF-Dependent Transcriptional and Tumorigenic Activity

Investigators identified NS8593, a negative gating modulator of the transient receptor potential cation channel TRPM7, as a novel inhibitor of myocardin-related transcription factor (MRTF)-A nuclear localization and transcriptional activity. [Oncogene] Abstract

miRNA-150-5p Promotes Hepatic Stellate Cell Proliferation and Sensitizes Hepatocyte Apoptosis during Liver Fibrosis

To explore the role of miRNA-150-5p in liver fibrosis, miRNA expression profiles, CCl₄-induced liver fibrosis progression and regression rodent models, quantitative real-time PCR, miR-150-5p mimics and inhibitors, cell proliferation and apoptosis detection, RNA sequencing and bioinformatics analysis were employed. [Epigenomics] Abstract | Graphical Abstract

Rat Liver Epigenome Programming by Perinatal Exposure to 2,2′,4′4′-Tetrabromodiphenyl Ether

Expression of small RNA and changes in DNA methylation in livers of adult rats were analyzed following perinatal exposure to 2,2′,4,4′-tetrabromodiphenyl ether, the polybrominated diphenyl ether congener most prevalent in human tissues. [Epigenomics] Abstract

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Autophagy in Hepatic Adaptation to Stress

The authors critically discuss the importance of functional autophagy for hepatic physiology, as well as the mechanisms whereby defects in autophagy cause liver disease. [J Hepatol] Abstract

Organoids for Liver Stage Malaria Research

Liver-derived organoids should fulfill a gap in Plasmodium liver infection models by providing a host culture which better recapitulates in vivo physiology than commonly used cell lines. [Trends Parasitol] Abstract

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

China National Medical Products Administration Approves Vosevi^® (Sofosbuvir, Velpatasvir and Voxilaprevir) for People with Chronic Hepatitis C Infection Who Require Re-Treatment

Gilead Sciences, Inc. announced that the China National Medical Products Administration has approved Vosevi^®, a once-daily single-tablet regimen for the treatment of chronic hepatitis C virus infection in adults without cirrhosis or with compensated cirrhosis who have failed prior treatment with a direct-acting antiviral therapy. [Gilead Sciences, Inc.] Press Release

Arrowhead Pharmaceuticals Doses First Patient in AROAAT2002 Open Label Phase II Study of ARO-AAT for Treatment of Alpha-1 Liver Disease

Arrowhead Pharmaceuticals Inc. announced that it has dosed the first patient in AROAAT2002, an open-label Phase II clinical study of ARO-AAT, the company’s second generation investigational RNA interference therapeutic being developed as a treatment for the rare genetic liver disease associated with alpha-1 antitrypsin deficiency. [Arrowhead Pharmaceuticals, Inc.] Press Release

2020 US Spending Bill Restricts Some Animal Research, Pushes for Lab Animal Retirement

Federal research agencies will be under increased pressure to reduce their use of monkeys, dogs, and cats when President Donald Trump signs the final 2020 US spending bill. [ScienceInsider] Editorial

The Top Retractions of 2019

Another year, another 1,433 (and counting) retractions. The tenth year of Retraction Watch’s existence included-as is often the case – a new record, some impressive numbers, and some bizarre stories. But it also included some exemplary behavior. [The Scientist] Editorial

NEW 3^rd Global NASH Congress
February 10-11, 2020
London, United Kingdom

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

NEW Postdoctoral Position – Molecular Regulators of Liver Function (Karolinska Institutet)

NEW Postdoctoral Fellowship – Immunopathogenesis (Institut Pasteur of Shanghai)

Lab Technician – Immunometabolism (Karolinska Institutet)

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

Professor – Hepatology (Jena University Hospital)

Postdoctoral Researcher – HIV and the Liver (Seattle’s Children’s Hospital)

Postdoctoral Researcher – Oncogenic Pathways (University of Liège)

Faculty Member – Pathogen-Associated Malignancies (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Drug-Induced Liver Injury (Johnson & Johnson)

Postdoctoral Researcher – Personalized Medicine (Mayo Clinic Center for Individualized Medicine)

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