Muscle Cell News Volume 4.21 | Jun 17 2019

TOP STORY

Genetic Tracing Identifies Early Segregation of the Cardiomyocyte and Non-Myocyte Lineages

Investigators quantified the lineage conversion of non-cardiomyocytes to cardiomyocytes in embryonic and neonatal hearts; and determined when the two cell lineages segregated during heart development. Moreover, they directly tested if non-myocyte to cardiomyocyte conversion contributed to neonatal heart regeneration. [Circ Res] Abstract

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CARDIAC MUSCLE CELLS

FNDC5 Alleviates Oxidative Stress and Cardiomyocyte Apoptosis in Doxorubicin-Induced Cardiotoxicity via Activating AKT

Scientists investigated the role and underlying mechanism of fibronectin type III domain-containing 5 (FNDC5) on oxidative stress and cardiomyocyte apoptosis in doxorubicin (DOX)-induced cardiotoxicity. Cardiomyocyte-specific FNDC5 overexpression was achieved using an adeno-associated virus system, and then the mice were exposed to a single intraperitoneal injection of DOX to generate DOX-induced cardiotoxicity. [Cell Death Differ] Full Article

Deletion of Heat Shock Protein 60 in Adult Mouse Cardiomyocytes Perturbs Mitochondrial Protein Homeostasis and Causes Heart Failure

The authors utilized an in vitro system to assess the effects of heat shock protein 60 (HSP60) deletion on mitochondrial protein import and protein stability after import, and found that both HSP60-dependent and HSP60-independent mitochondrial proteins could be normally imported in mutant mitochondria. However, the former underwent degradation in mutant mitochondria after import, suggesting that the protein exhibited low stability in mutant mitochondria. [Cell Death Differ] Full Article

HAND2-Mediated Epithelial Maintenance and Integrity in Cardiac Outflow Tract Morphogenesis

Researchers revealed a gradient of HAND2 protein in the cardiac progenitors in the anterior dorsal pericardial wall and adjacent transition zone (TZ) in the outflow tract. Deletion of Hand2 caused cell arrest and accumulation in the TZ leading to defective morphogenesis. [Development] Abstract

Ttc39c Is Upregulated during Skeletal Muscle Atrophy and Modulates ERK1/2 MAP Kinase and Hedgehog Signaling

Expression analysis using quantitative polymerase chain reaction and Western blots revealed that tetratricopeptide repeat domain containing 39cm (Ttc39c) was expressed in both proliferating and differentiated muscle cells, peaking during early differentiation and then decreasing as cells progress further through the differentiation process. To further analyze the transcriptional regulation of Ttc39c, promoter fragments of the gene were cloned and fused with the secreted alkaline phosphatase reporter gene. [J Cell Physiol] Abstract

SKELETAL MUSCLE CELLS

The Transcription Factor Slug Represses p16^Ink4a and Regulates Murine Muscle Stem Cell Aging

Researchers report that the zinc-finger transcription factor Slug was highly expressed in quiescent satellite cells (SCs) of mice and functioned as a direct transcriptional repressor of p16^Ink4a. Loss of Slug promoted derepression of p16^Ink4a in SCs and accelerated the entry of SCs into a fully senescent state upon damage-induced stress. [Nat Commun] Full Article

SMOOTH MUSCLE CELLS

Cellular Effects of Butyrate on Vascular Smooth Muscle Cells Are Mediated through Disparate Actions on Dual Targets, Histone Deacetylase (HDAC) Activity and PI3K/Akt Signaling Network

Using proliferating vascular smooth muscle cells (VSMCs) exposed to 5mM butyrate, immunoblotting studies were performed to determine whether PI3K/Akt pathway that regulated different cellular effects was a target of butyrate-induced VSMC growth. Butyrate inhibited phosphorylation-dependent activation of PI3K, PDK1, and Akt, eliciting differential effects on downstream targets of Akt. [Int J Mol Sci] Full Article

Foxc1 Is Required for Embryonic Head Vascular Smooth Muscle Differentiation in Zebrafish

Using timelapse imaging, investigators observed that foxc1b expressing mesenchymal cells differentiated into acta2 expressing vascular mural cells. They showed that in zebrafish, while foxc1b was co-expressed in acta2 positive smooth muscle cells that associated with large diameter vessels, it was not co-expressed in capillaries where pdgfrβ positive pericytes were located. [Dev Biol] Abstract

Hydrogen Sulfide Inhibited L-Type Calcium Channels (CaV1.2) via Up-Regulation of the Channel Sulfhydration in Vascular Smooth Muscle Cells

Researchers ascertained whether hydrogen sulfide (H2S) affected L-type calcium (Ca²⁺) channels in vascular smooth muscle cells and the subsequent signaling pathways. CaV1.2L-type Ca²⁺ currents were inhibited by sodium hydrosulfide in A7r5 cell lines using the whole-cell patch-clamp technique. [Eur J Pharmacol] Abstract

Circ_RUSC2 Upregulates the Expression of miR-661 Target Gene SYK and Regulates the Function of Vascular Smooth Muscle Cells

Detection of circRNA expression in different vascular smooth muscle cells (VSMCs) phenotypes revealed that circ_RUSC2 was upregulated in proliferative VSMCs. Sequence analysis of circ_RUSC2 showed that there were multiple binding sites of miR-661 on circ_RUSC2, and SYK was an important target gene of miR-661. [Biochem Cell Biol] Abstract

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G Protein-Coupled Receptor Kinases As Therapeutic Targets in the Heart

Investigators discuss the G protein-coupled receptors (GPCR) signaling pathways and the GPCR kinases (GRKs) involved in the pathophysiology of heart disease. Given that increased expression and activity of GRK2 and GRK5 contribute to the loss of contractile reserve in the stressed and failing heart, inhibition of overactive GRKs has been proposed as a novel therapeutic approach to treat heart failure. [Nat Rev Cardiol] Abstract

Looking beyond PGC-1α: Emerging Regulators of Exercise-Induced Skeletal Muscle Mitochondrial Biogenesis and Their Activation by Dietary Compounds

The authors highlight the regulatory mechanisms by which nuclear factor erythroid 2-related factor 2, estrogen-related receptor gamma, PPARβ and leucine-rich pentatricopeptide repeat-containing protein may contribute to the control of skeletal muscle mitochondrial biogenesis. They also present evidence supporting/refuting the ability of sulforaphane, quercetin, and epicatechin to promote skeletal muscle mitochondrial biogenesis and their potential to augment mitochondrial training adaptations. [Appl Physiol Nutr Metab] Abstract

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Wave Life Sciences to Present at Parent Project Muscular Dystrophy 2019 Annual Conference

Wave Life Sciences Ltd announced that Michael Panzara, MD, MPH, Chief Medical Officer, will give a presentation that will include an overview of the ongoing clinical development of suvodirsen, the company’s investigational stereopure oligonucleotide for boys with Duchenne muscular dystrophy who are amenable to exon 51 skipping. [Press release from Wave Life Sciences discussing research presented at the Parent Project Muscular Dystrophy (PPMD) 2019 Annual Conference, Orlando] Press Release

ZOLL Signs Definitive Agreement to Purchase Cardiac Science

ZOLL^® Medical Corporation announced it has signed a definitive agreement to purchase Cardiac Science Corporation, a leading provider of automated external defibrillators, related services, and accessories. [ZOLL Medical Corporation] Press Release

Vertex Expands into New Disease Areas and Enhances Gene Editing Capabilities through Expanded Collaboration with CRISPR Therapeutics and Acquisition of Exonics Therapeutics

Vertex Pharmaceuticals Incorporated announced that the company is enhancing its gene editing capabilities to develop novel therapies for Duchenne muscular dystrophy and myotonic dystrophy type 1 by expanding its collaboration with CRISPR Therapeutics and acquiring Exonics Therapeutics. [Vertex Pharmaceuticals Incorporated] Press Release

MDA Awards Venture Philanthropy Grant to Locana to Develop Novel Treatment for Muscular Dystrophy

The Muscular Dystrophy Association and Locana, a leading RNA-targeting gene therapy company, announced the award of an MDA Venture Philanthropy grant totaling $550,000 to advance Locana’s development program for myotonic dystrophy. [The Muscular Dystrophy Association] Press Release

Harassment Common for National Institutes of Health Employees

More than one-fifth of people who work for the National Institutes of Health and who responded to a survey by the agency have experienced some form of harassment during the last year, according to an interim report the agency published on June 12. Of nearly 16,000 respondents, 10 percent reported that they had experienced unwanted sexual attention, while 18 percent said they had been subject to gender harassment. [The Scientist] Editorial

China Announces Hefty Fines for Unauthorized Collection of DNA

China announced a new law restricting the collection and use of genetic resources from people in the country — including biological samples that yield DNA, such as blood, and data gleaned from sequencing them. There will be hefty fines for unauthorized collection or use of genetic material. [Nature News] Editorial

NEW Frontiers in Myogenesis
September 23-28, 2019
San Jose, Costa Rica

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NEW Postdoctoral Researcher – Muscle Atrophy and Metabolism (McGill University)

Postdoctoral Researchers – Cardiovascular Studies (Virginia Tech)

Postdoctoral – Proteomics of Muscles and Aging (Oklahoma Medical Research Foundation)

Postdoctoral Fellow – Facioscapulohumeral Muscular Dystrophy Research (Pfizer)

Postdoctoral Fellow – Cardiac and Skeletal Muscle Engineering (Georgia Institute of Technology & Emory University School of Medicine)

Postdoctoral Fellow – Muscular Growth, Wasting, and Dystrophy (University of Louisville)

Postdoctoral Fellow – Cardiovascular Epidemiology (Boston University School of Medicine)

Postdoctoral Fellow – Molecular Cardiology (University of Illinois at Chicago)

Assistant Professor – Sarcoma or Skeletal Related Malignancies (University of California, Davis)

Assistant Specialist – Cardiovascular Research (University of California, Davis)

Assistant/Associate Adjunct Professor – Cardiovascular Medicine (University of California, Davis)

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