Muscle Cell News Volume 2.17 | May 15 2017

TOP STORY

Intermittent Glucocorticoid Steroid Dosing Enhances Muscle Repair without Eliciting Muscle Atrophy

Investigators tested steroid dosing in mice and found that a single pulse of glucocorticoid steroids improved sarcolemmal repair through increased expression of annexins A1 and A6, which mediate myofiber repair. This increased expression was dependent on glucocorticoid response elements upstream of annexins and was reinforced by the expression of forkhead box O1. [J Clin Invest] Full Article | Press Release

(Ranked by impact factor of the journal)

CARDIAC MUSCLE CELLS

Regulation of Cardiomyocyte Behavior in Zebrafish Trabeculation by Neuregulin 2a Signaling

Reseachers addressed two fundamental, yet unresolved, questions about cardiac trabeculation: why does it initially occur in the ventricle and not the atrium, and how is it modulated by blood flow/contractility. Using loss-of-function approaches, they showed that zebrafish Neuregulin 2a is required for trabeculation, and using a protein-trap line, found that it is expressed in both cardiac chambers with different spatiotemporal patterns. [Nat Commun] Full Article

Differentiation of Cardiomyocytes and Generation of Human Engineered Heart Tissue

Human induced pluripotent stem cells (hiPSC)-derived cardiomyocytes are often assessed in single-cell assays. A shortcoming of these assays is the limited ability to characterize the physiological parameters of cardiomyocytes, such as contractile force, due to random orientations. This protocol describes the differentiation of cardiomyocytes from hiPSCs, which occurs within 14 days. After casting, cardiomyocytes undergo 3D assembly. This produces fibrin-based engineered heart tissues—in a strip format—that generate force under auxotonic stretch conditions. [Nat Protoc] Abstract

Circular RNA Mediates Cardiomyocyte Death via miRNA-Dependent Upregulation of MTP18 Expression

Scientists showed that a circular RNA (circRNA) regulates mitochondrial fission and apoptosis in the heart by directly targeting and downregulating miR-652-3p; this in turn blocks mitochondrial fission and cardiomyocyte cell death by suppressing MTP18 translation. [Cell Death Differ] Abstract

Cardiosphere-Derived Cells Require Endoglin for Paracrine-Mediated Angiogenesis

In endothelial cells endoglin regulates angiogenic responses, the authors hypothesized that endoglin is required to promote the paracrine pro-angiogenic properties of cardiosphere-derived-cells (CDCs). Cre/LoxP technology was used to genetically manipulate endoglin expression in CDCs, and they found that the pro-angiogenic properties of the CDC secretome are endoglin dependent both in vitro and in vivo. [Stem Cell Reports] Full Article

SKELETAL MUSCLE CELLS

Consequences of MEGF10 Deficiency on Myoblast Function and Notch1 Interactions

Scientists demonstrated that short hairpin RNA-mediated knockdown of Megf10, as well as overexpression of the pathogenic human p.C774R mutation, lead to impaired proliferation and migration of C2C12 cells. [Hum Mol Genet] Abstract

Diagnostic Anoctamin-5 Protein Defect in Patients with ANO5-Mutated Muscular Dystrophy

Researchers aimed to specify ANO5 protein expression in human skeletal muscle, and to investigate if the ANO5 protein levels are affected by different ANO5 mutations in anoctaminopathy patients. [Neuropathol Appl Neurobiol] Abstract

Mechanically Patterned Neuromuscular Junctions-in-a-Dish Have Improved Functional Maturation

Neuromuscular junctions (NMJ)-in-a-dish models have been developed to examine human motor neuron-associated dysfunction with disease; however such co-culture models have randomly oriented myotubes with immature synapses that contract asynchronously. Mechanically patterned extracellular matrix with alternating soft and stiff stripes improve current NMJ-in-a-dish models by inducing both mouse and human myoblast durotaxis to stripes where they aligned, differentiated, and fused into patterned myotubes. [Mol Biol Cell] Abstract | Full Article

SMOOTH MUSCLE CELLS

Golgi-Independent Routes Support Protein Disulfide Isomerase Externalization in Vascular Smooth Muscle Cells

The authors showed that vascular smooth muscle cells display a robust cell-surface (cs) protein disulfide isomerase-A1 pool, which binds to cs independently of electrostatic forces. [Redox Biol] Abstract

Janus Kinase 3, a Novel Regulator for Smooth Muscle Proliferation and Vascular Remodeling

The molecular mechanism underlying smooth muscle cell (SMC) proliferation is not completely understood. The authors aimed to determine the role and mechanism of Janus kinase 3 in vascular remodeling and SMC proliferation. [Arterioscler Thromb Vasc Biol] Abstract

Targeting Wnt/β-Catenin Activated Cells with Dominant-Negative N-Cadherin to Reduce Neointima Formation

Investigators examined whether a gene therapy approach that selectively kills Wnt/β-catenin/T cell factor (TCF) activated vascular smooth muscle cells (VSMCs) using dominant-negative N-cadherin (dn-N-cadherin) reduced intimal thickening. Cultured human VSMCs infected with an adenovirus encoding dn-N-cadherin via the TCF promoter specifically expressed dn-N-cadherin in response to activation of the Wnt/β-catenin/TCF pathway. [Mol Ther Methods Clin Dev] Full Article | Graphical Abstract

Gene Expression Profiling Discerns Molecular Pathways Elicited by Ligand Signaling to Enhance the Specification of Embryonic Stem Cells into Skeletal Muscle Lineage

The authors review how several signaling molecules involved in the progression of myogenic specification and commitment are differentially regulated by bexarotene and retinoic acid, suggesting that early targets of rexinoid allow the coordinated regulation of molecular events which leads to efficient myogenic differentiation in embryonic stem cells. [Cell Biosci] Full Article

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

New Preclinical Data Support SGT-001 as a Novel Treatment Approach for Duchenne Muscular Dystrophy

Solid Biosciences announced that new data from two preclinical studies reinforce the potential of its investigational microdystrophin gene therapy, SGT-001, to be an effective treatment approach for Duchenne muscular dystrophy. [Press release from Solid Biosciences discussing research presented at the American Society of Gene and Cell Therapy (ASGCT) 20^th Annual Meeting, Washington D.C.] Press Release

Capricor Therapeutics Provides Update on ALLSTAR Trial

Capricor Therapeutics, Inc. announced that a pre-specified administrative interim analysis performed on six-month follow-up data from the ALLSTAR Trial, an ongoing randomized, double-blind, placebo-controlled, 142-patient Phase II clinical trial of CAP-1002 (allogeneic cardiosphere-derived cells) in adults who have experienced a large heart attack with residual cardiac dysfunction, has demonstrated a low probability of achieving a statistically-significant difference in the 12-month primary efficacy endpoint of percent change from baseline infarct size as a percent of left ventricular mass, measured by cardiac magnetic resonance imaging. [Capricor Therapeutics, Inc.] Press Release

New Japan-Originated ALS Treatment Option Available to Patients in the U.S.

Mitsubishi Tanabe Pharma Corporation’s Radicava^TM has been approved by the FDA as a treatment for amyotrophic lateral sclerosis (ALS) and is expected to be available in the US by August. The intravenous drug, given in addition to standard of care, reduced the functional decline rate in ALS patients by about a third after six months of treatment. [Mitsubishi Tanabe Pharma Corporation] Press Release

Revamped ‘Anti-Science’ Education Bills in United States Find Success

State and local legislatures in the United States are experimenting with new ways to target the topics taught in science classes, and it seems to be paying dividends. Florida’s legislature approved a bill that would enable residents to challenge what educators teach students [Nature News] Editorial

China Cracks Down on Fake Data in Drug Trials

Those who submit faked clinical trial data might now go to jail — and in extreme circumstances, be executed — under a new interpretation of China’s criminal code. The policy shift is one of a handful of measures that China is implementing both to speed up its notoriously slow drug-approval process and to keep dangerous and ineffective drugs off the market. [Nature News] Editorial

The Secret War against Counterfeit Science

China is famous for knock-off DVDs, Louis Vuitton bags and Rolex watches. But counterfeit reagents aren’t on sale in busy public markets. They are sold through sophisticated websites, mixed in with legitimate supplies, and sourced and sold using a network of unwitting partners. [Nature News] Editorial

Science Publishers Try New Tack to Combat Unauthorized Paper Sharing

The unauthorized sharing of copyrighted research papers is on the rise, say analysts who track the publishing industry. Faced with this problem, science publishers seem to be changing tack in their approach to researchers who breach copyright. [Nature News] Editorial

NEW Gordon Research Conferences: Cell Growth & Proliferation
July 9-14, 2017
Mount Snow, Vermont, United States

NEW Ion Channel Regulation
July 9-14, 2017
Steamboat Springs, Colorado, United States

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

NEW Postdoctoral Position(s) – Skeletal Muscle Stem Cells (Inserm)

Postdoctoral Associate – Genetics of Muscular Dystrophy (University of Florida College of Medicine)

Postdoctoral/ Graduate Student Positions – Neuromuscular Diseases (University of Alberta)

PhD Studentship – Experimental Genetic Cardiology (Oslo University Hospital)

Postdoctoral Position(s) – Skeletal and Cardiac Muscle Disease Modeling and Regeneration (Duke University)

Research Fellow – Cardiovascular Science (Columbia University)

International PhD Program – Biomedical Research (Institute of Genetics & Molecular & Cellular Biology/CERBM GIE)

Principal Investigator – Human Physiology and Experimental Medicine (University of Cambridge)

Postdoctoral Fellow – Vascular Smooth Muscle (The University of Tennessee Health Science Center)

Postdoctoral Fellowship – Heart Regeneration (Children’s Hospital Los Angeles – University of Southern California)

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