Muscle Cell News Volume 4.18 | May 27 2019

TOP STORY

Proteasome-Dependent Regulation of Distinct Metabolic States during Long-Term Culture of Human iPSC-Derived Cardiomyocytes

Researchers combined transcriptomic sequencing with pathway network mapping in induced pluripotent stem cell (iPSC) derived-cardiomyocytes (CMs) that were cultured until a late time point, day 200, in comparison to a medium time point, day 90, and an early time point, day 30. Transcriptomic landscapes of long-term cultured iPSC-CMs allowed mapping of distinct metabolic stages during development of maturing iPSC-CMs. [Circ Res] Abstract

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CARDIAC MUSCLE CELLS

Biomimetic Electromechanical Stimulation to Maintain Adult Myocardial Slices In Vitro

The authors investigated the role of electromechanical stimulation in preventing culture-induced dedifferentiation of adult cardiac tissue using rat, rabbit and human heart failure myocardial slices. They report that the application of a preload equivalent to sarcomere length =2.2μm was optimal for the maintenance of rat myocardial slice structural, functional and transcriptional properties at 24 hours. [Nat Commun] Full Article

Hand2 Selectively Reorganizes Chromatin Accessibility to Induce Pacemaker-Like Transcriptional Reprogramming

Investigators explored the role of Hand2 in induced pacemaker-like myocytes (iPM) formation by using a combination of transcriptome, genome, and biochemical assays. They found many shared transcriptional signatures between iPMs and the endogenous sinoatrial node, yet key regulatory networks remained missing. They demonstrated that Hand2 augmented chromatin accessibility at loci involved in sarcomere organization, electrical coupling, and membrane depolarization. [Cell Rep] Full Article | Graphical Abstract

Using Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes as a Model to Study Trypanosoma cruzi Infection

Scientists modeled Chagas disease using human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) to understand the complex interplay between the parasite Trypanosoma cruzi and host cells. They showed that iPSC-CMs could get infected with the T. cruzi Y strain and that all parasite cycle stages could be identified in their model system. [Stem Cell Reports] Full Article

Epigenetic Priming of Human Pluripotent Stem Cell-Derived Cardiac Progenitor Cells Accelerates Cardiomyocyte Maturation

Cardiac progenitor cells (CPCs) were differentiated from human pluripotent stem cells (hPSCs) using a monolayer differentiation protocol with defined small molecule Wnt temporal modulation, and polycytidylic acid (pIC) was added during the formation of early CPCs. pIC priming did not alter the expression of cell surface markers for CPCs, expression of common cardiac transcription factors, or final purity of differentiated hPSC-derived cardiomyocytes. [Stem Cells] Abstract | Press Release

SKELETAL MUSCLE CELLS

A 3D Culture Model of Innervated Human Skeletal Muscle Enables Studies of the Adult Neuromuscular Junction

Scientists described a three-dimensional (3D) co-culture method whereby human muscle progenitors mixed with human pluripotent stem cell-derived motor neurons self-organized to form functional neuromuscular junction connections. Functional connectivity between motor neuron endplates and muscle fibers was confirmed with calcium imaging and electrophysiological recordings. [eLife] Full Article

Smad7:β-Catenin Complex Regulates Myogenic Gene Transcription

Biochemical analysis identified a Smad7 interaction domain between aa575 and aa683 of β-catenin. Reporter gene analysis and chromatin immunoprecipitation demonstrated that Smad7 and β-catenin were cooperatively recruited to the extensively characterized ckm promoter proximal region to facilitate its muscle restricted transcriptional activation in myogenic cells. [Cell Death Dis] Full Article | Press Release

Treatment of Volumetric Muscle Loss in Mice Using Nanofibrillar Scaffolds Enhances Vascular Organization and Integration

Investigators fabricated engineered skeletal muscle composed of myotubes interspersed with vascular endothelial cells using spatially patterned scaffolds that induce aligned cellular organization, and then assessed their therapeutic benefit for treatment of murine volumetric muscle loss. [Commun Biol] Full Article

SMOOTH MUSCLE CELLS

Targeting Cyclin-Dependent Kinases for the Treatment of Pulmonary Arterial Hypertension

Scientists screened for pathways that may be responsible for the abnormal phenotype of pulmonary arterial smooth muscle cells, a major contributor of pulmonary arterial hypertension (PAH) pathobiology, and identified cyclin-dependent kinases (CDKs) as overactivated kinases in specimens derived from patients with idiopathic PAH. This increased CDK activity was confirmed at the level of mRNA and protein expression in human and experimental PAH, respectively. [Nat Commun] Full Article

H19 LncRNA Identified as a Master Regulator of Genes That Drive Uterine Leiomyomas

Researchers report that the expression of H19 long noncoding RNA (lncRNA) was aberrantly increased in uterine leiomyomas or fibroids. Using cell culture and genome-wide transcriptome and methylation profiling analyses, they demonstrated that H19 promoted expression of MED12, HMGA2, and key extracellular matrix-remodeling genes via multiple mechanisms including a new class of epigenetic modification by TET3. [Oncogene] Full Article

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O-GlcNAcylation as a Regulator of the Functional and Structural Properties of the Sarcomere in Skeletal Muscle: An Update Review

The authors focus on myofibrillar proteins, including contractile and structural proteins. Because of the modification of motor and regulatory proteins, the regulatory myosin light chain is related to several reports that support a key role of O-GlcNAcylation in the fine modulation of calcium activation parameters of skeletal muscle fibers, depending on muscle phenotype and muscle work. [Acta Physiol] Abstract

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Applied Therapeutics to Present Data Highlighting AT-001, a Novel, Potent and Selective Aldose Reductase Inhibitor for Treatment of Diabetic Cardiomyopathy

Applied Therapeutics Inc. announced that two data presentations will be displayed. Both presentations highlight AT-001, a novel, potent and selective aldose reductase inhibitor in clinical development for diabetic cardiomyopathy. [Press release from Applied Therapeutics discussing research to be presented at the European Society for Cardiology 6^th World Congress on Acute Heart Failure, Athens] Press Release

Santhera Starts Collaboration in Gene Therapy Research for Congenital Muscular Dystrophy with the Biozentrum, University of Basel, Co-Financed by Innosuisse

Santhera Pharmaceuticals announced its collaboration with the Biozentrum of the University of Basel to advance gene therapy research for the treatment of LAMA2-deficient congenital muscular dystrophy. The program is supported by public funding for innovation in Switzerland through a grant from Innosuisse – the Suisse Innovation Agency. Innosuisse and Santhera will jointly invest CHF 1.2 million into this preclinical research collaboration. [Santhera Pharmaceuticals] Press Release

AveXis Receives FDA Approval for Zolgensma®, the First and Only Gene Therapy for Pediatric Patients with Spinal Muscular Atrophy (SMA)

AveXis announced the FDA has approved Zolgensma^® for the treatment of pediatric patients less than two years of age with SMA with bi-allelic mutations in the survival motor neuron 1 gene. [AveXis] Press Release

Biogen’s Spinraza^® (Nusinersen) Receives Positive Recommendation from Nice for Funding in the United Kingdom for the Treatment of Infants, Children and Adults with Spinal Muscular Atrophy

Biogen Inc. announced that The National Institute for Health and Care Excellence in the United Kingdom has recommended funding for Spinraza^® on the National Health Service. The positive recommendation is for the treatment of infants, children and adults with 5q spinal muscular atrophy (SMA), including pre-symptomatic and symptomatic SMA Types 1, 2 and 3. [Biogen Inc.] Press Release

MyoKardia Announces Inaugural MyoSeeds™ Research Grants Program Awardees

MyoKardia announced the award of $750,000 divided among three innovative research projects through the first cycle of its MyoSeeds™ Research Grants Program. MyoSeeds is MyoKardia’s initiative intended to support original, independent research in the biology and underlying mechanisms of cardiomyopathies, and approaches to precision heart disease treatment as part of the company’s mission to change the world for people with serious cardiovascular diseases. [MyoKardia] Press Release

Cell Scientist Rebecca Berdeaux Awarded $1.9 Million by NIH to Research Muscle Regeneration

A scientist with The University of Texas Health Science Center at Houston is working to enhance the body’s ability to repair damaged skeletal muscle. The research is supported with a $1.9 million grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health (NIH). [The University of Texas Health Science Center at Houston] Press Release

Reducing the Destruction of Heart Failure

A University of Houston College of Pharmacy researcher is characterizing a potential therapeutic target to increase heart function following a heart attack, helping alleviate the symptoms of heart failure. The National Heart, Lung, and Blood Institute awarded $459,000 to associate professor of pharmacology Bradley K. McConnell to do the work which involves the actions of adrenaline/noradrenaline on the heart. [The University of Houston] Press Release

Parent Project Muscular Dystrophy Awards $100,000 Grant to UCLA to Map the Immune Phenotype in Duchenne Muscular Dystrophy

Parent Project Muscular Dystrophy announced that Dr. Carrie Miceli from the Center for Duchenne Muscular Dystrophy at University of California – Los Angeles (UCLA) is the recipient of a $100,000 grant to continue her work to immuno-phenotype cells from people living with Duchenne, Becker, and control patients. [Parent Project Muscular Dystrophy] Press Release

Taiwan Considers Double-Blind Peer Review for Grants

Taiwan’s science ministry is thinking of introducing double-blind peer review to assess research-grant proposals, a trend being adopted by some journals to eliminate bias. [Nature News] Editorial

Brazilian Scientists Strive to Turn Politicians Into Allies

Brazil’s scientists are fighting back against President Jair Bolsonaro’s plans to slash funding for research and education programs. Researchers have joined with members of Brazil’s legislature, the National Congress, to highlight the strategic role that science, technology, and education play in the country’s economic and social development. [Nature News] Editorial

How European Scientists Will Spend €100 Billion

Politicians don’t win prizes for speed, but the European Union’s parliament and the leaders of its member states made record time this year when they hammered out an agreement that could supply researchers in Europe with more than €100 billion (US$113 billion) over seven years. [Nature News] Editorial

NEW Bone and Muscle Interactions: The Mechanical and Beyond
August 16-18, 2019
Indianapolis, Indiana, United States

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NEW Postdoctoral Fellow – Facioscapulohumeral Muscular Dystrophy Research (Pfizer)

NEW 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 Researcher – Metainflammation in Muscle, Liver, or Adipose Biology (Case Western Reserve University)

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

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

Senior Research Investigator – Multiple Sclerosis Research (Thomas Jefferson University)

Postdoctoral Positions – Signaling Mechanisms of Muscle Metabolism and Regeneration (McGovern Medical School at University of Texas Health Science Center)

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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