Muscle Cell News Volume 2.32 | Sep 25 2017

TOP STORY

Macrophage-Released ADAMTS1 Promotes Muscle Stem Cell Activation

The authors showed that macrophages at sites of muscle injury induced activation of satellite cells via expression of Adamts1. Overexpression of Adamts1 in macrophages in vivo was sufficient to increase satellite cell activation and improve muscle regeneration in young mice. [Nat Commun] Full Article

(Ranked by impact factor of the journal)

CARDIAC MUSCLE CELLS

CRISPR Correction of the PRKAG2 Gene Mutation in the Patient’s iPSC-Derived Cardiomyocytes Eliminates the Electrophysiological and Structural Abnormalities

Mutations in the PRKAG2 gene encoding the γ-subunit of adenosine monophosphate-kinase cause hypertrophic cardiomyopathy and familial-Wolff-Parkinson-White syndrome. Using the CRISPR technology, researchers corrected the mutation and generated isogenic induced pluripotent stem cell (iPSC)-derived cardiomyocytes. [Heart Rhythm] Abstract

Ventricular Myocardium Development and the Role of Connexins in the Human Fetal Heart

Scientists employed diffusion tensor magnetic resonance imaging to explore the architecture and tissue organization of the developing heart aged 95–143 DGA. They showed that fractional anisotropy increased, diffusion coefficients decreased, and fiber paths, extracted by tractography, increased linearly with gestation, indicative of the increasing organization of the ventricular myocytes. [Sci Rep] Full Article

Notch Signaling Modulates the Electrical Behavior of Cardiomyocytes

Investigators tested the possibility that Notch signaling modulates electrical behavior of cardiomyocytes by interfering with Kv currents. In cultured neonatal myocytes, inhibition of the proteolitic release of Notch1 intracellular domain with a γ-secretase antagonist increased transcript levels of the Kv channel-interacting proteins 2 and enhanced the density of Kv currents. [Am J Physiol Heart Circ Physiol] Abstract

SKELETAL MUSCLE CELLS

The Histone Deacetylase SIRT6 Blocks Myostatin Expression and Development of Muscle Atrophy

Researchers report that SIRT6 depletion in cardiac as well as skeletal muscle cells promotes myostatin expression. They also observed upregulation of other factors implicated in muscle atrophy, such as angiotensin-II, activin and Acvr2b, in SIRT6 depleted cells. [Sci Rep] Full Article

Casein Kinase 2-Mediated Phosphorylation of Brahma-Related Gene 1 Controls Myoblast Proliferation and Contributes to SWI/SNF Complex Composition

Scientists report that brahma-related gene 1 (Brg1) is a target of casein kinase 2, a serine/threonine kinase, in proliferating myoblasts. While BRG1-deleted myoblasts that ectopically express the SA-Brg1 mutant proliferated similarly to the parental cells or cells ectopically expressing wildtype Brg1, ectopic expression of the SE-Brg1 mutant reduced proliferation and increased cell death, similar to observations from cells lacking Brg1. [J Biol Chem] Abstract | Full Article

Microgravity Influences Maintenance of the Human Muscle Stem/Progenitor Cell Pool

The authors used induced pluripotent stem cell-derived human skeletal muscle stem/progenitor cells (SMPCs) to investigate the effect of microgravity on maintenance of the stem/progenitor cell pool. Human SMPCs were induced by free-floating spherical aggregation culture, and derivatized-SMPC spheres were maintained in a microgravity condition for two weeks using a clinostat rotation system. [Biochem Biophys Res Commun] Full Article

SMOOTH MUSCLE CELLS

Vascular Smooth Muscle Cells Derived from Inbred Swine Induced Pluripotent Stem Cells for Vascular Tissue Engineering

Highly enriched, functional vascular smooth muscle cells were derived from swine induced pluripotent stem cells based on addition of ascorbic acid and inactivation of reprogramming factor via doxycycline withdrawal. [Biomaterials] Abstract

Microtubule Structures Underlying the Sarcoplasmic Reticulum Support Peripheral Coupling Sites to Regulate Smooth Muscle Contractility

Researchers investigated the role of the cytoskeleton in maintaining peripheral coupling and associated Ca²⁺ signaling networks within native smooth muscle cells of mouse and rat cerebral arteries. [Sci Signal] Abstract

Chebulinic Acid Inhibits Smooth Muscle Cell Migration by Suppressing PDGF-Rβ Phosphorylation and Inhibiting Matrix Metalloproteinase-2 Expression

Scientists investigated the inhibitory effect of chebulinic acid (CBA) on cell migration and matrix metalloproteinase-2 activation in platelet-derived growth factor (PDGF)-BB-induced mouse and human vascular smooth muscle cells (VSMCs). CBA significantly inhibited PDGF-BB-induced migration in mouse and human VSMCs, without inducing cell death. [Sci Rep] Full Article

Reverse Remodeling and Myocardial Recovery in Heart Failure

Researchers summarize the latest findings on reverse remodeling and myocardial recovery. Accumulating evidence shows that the molecular changes associated with heart failure, in particular in the transcriptome, metabalome, and extracellular matrix, persist in the reverse-remodelled myocardium despite apparent normalization of macrolevel properties. [Nat Rev Cardiol] Abstract

Role of Non-Coding RNAs in Regulation of Cardiac Cell Death and Cardiovascular Diseases

The authors focus on recent progress regarding the complex relationship between apoptosis/necrosis/autophagy and non-coding RNAs in the context of myocardial cell death in response to stress. [Cell Mol Life Sci] Abstract

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AMO Pharma Reports Update on Positive Interim Analysis for the First Cohort of Phase IIa Congenital Myotonic Dystrophy Study

AMO Pharma Limited provided an update with regard to the first cohort of its study of AMO-02 in congenital myotonic dystrophy. This Phase II exploratory study was designed to examine the safety and tolerability of two doses of AMO-02 in adults with congenital and juvenile onset myotonic dystrophy. [Press release from AMO Pharma Limited (PR Newswire Association LLC.) discussing research to be presented at the American Neurological Association’s (ANA) 2017 Annual Meeting, San Diego] Press Release

Synpromics Announces Gene Therapy Research Partnership with Solid Biosciences

Synpromics Ltd. announced a new research partnership with Solid Biosciences, LLC. Under the terms of the agreement, Synpromics will provide Solid Biosciences access to a set of key muscle-selective promoter candidates to be used in the development of new treatment options for Duchenne muscular dystrophy. [Synpromics Ltd.] Press Release

Summit Joins cTAP in Collaborative Effort to Enhance the Development of Utrophin Modulators and Other Treatments for Duchenne Muscular Dystrophy

Summit Therapeutics plc. announced it has joined the Collaborative Trajectory Analysis Project (‘cTAP’) to support cTAP’s mission of accelerating the development of drugs to treat Duchenne muscular dystrophy (DMD) through a coalition of Duchenne clinical experts, patient advocates and biopharmaceutical companies. [Summit Therapeutics plc.] Press Release

Amylyx Pharmaceuticals Receives FDA Orphan Drug Designation for AMX0035 for the Treatment of Amyotrophic Lateral Sclerosis

Amylyx Pharmaceuticals, Inc., announced that the FDA has granted orphan drug designation to AMX0035, an oral therapeutic in clinical development for the treatment of amyotrophic lateral sclerosis ALS. The Company recently began a Phase II clinical study, the CENTAUR trial, to evaluate the safety and efficacy of AMX0035 in ALS patients. [Amylyx Pharmaceuticals, Inc.] Press Release

What Germany’s Election Results Mean for Science

As Germany reels from an unexpected surge for the far right in the elections, researchers don’t expect much effect on the country’s generous support for science. But with smaller parties standing to gain political influence, battles over issues such as the regulation of gene-edited organisms and how to cut greenhouse-gas emissions could grow fiercer. [Nature News] Editorial

United Kingdom Sees Dip in European Research Applications after Brexit Vote

The number of researchers applying for Europe-funded Marie Curie fellowships in the United Kingdom has dipped slightly since the country’s vote to leave the European Union, data released to Nature show. But there is no evidence yet of a sharp collapse in interest, which some scientists had feared in the wake of the Brexit referendum. [Nature News] Editorial

HHMI’s Own Brand of Diversity in the Life Sciences

One of Erin O’Shea’s first moves as Howard Hughes Medical Institute (HHMI) president was committing $25 million a year to support postdocs from underrepresented groups. Her hope was that they would eventually change the color—and culture—of their departments as they moved into leadership positions, in addition to serving as role models for the next generation of scientists. [ScienceInsider] Editorial

NEW Keystone Symposia: Bioenergetics and Metabolic Disease
January 21-25, 2018
Keystone, Colorado, United States

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NEW Postdoctoral Associate – Skeletal Muscle Differentiation (University of Minnesota)

Postdoctoral Research Associate – Cardiovascular Regenerative Medicine (University of Cambridge)

Postdoctoral Research Positions – Molecular and Integrative Biology of Heart and Muscle (University of Minnesota Medical School)

Faculty Positions – Cardiovascular Biology (Oklahoma Medical Research Foundation)

Researcher – Skeletal Tissue Engineering (KU Leuven)

Research Assistant – Cardiovascular Stem Cells (University of Oxford)

Tenure-Track Assistant or Associate Professor – Human Cardiac and Cardiovascular Development (Columbia University Medical Center)

Postdoctoral Fellowship – Cardiology (Temple University)

Postdoctoral Research Fellow – Cardiovascular Experimental Therapeutics (University Health Network)

Scientist – Obesity, Metabolic & Muscle Diseases (Regeneron)

Postdoctoral Fellow – Diabetes and Heart Disease (University Health Network)

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