Muscle Cell News Volume 4.30 | Sep 9 2019

TOP STORY

Wnt4 from the Niche Controls the Mechano-Properties and Quiescent State of Muscle Stem Cells

Using cell-specific inducible genetics, investigators found that a Wnt4-Rho signaling axis constrained satellite cell (SC) numbers and activation during tissue homeostasis in adult mice. Wnt4 activated Rho in quiescent SCs to maintain mechanical strain, restrict movement in the niche, and repress YAP. [Cell Stem Cell] Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

CARDIAC MUSCLE CELLS

Profiling Chromatin States Using Single-Cell itChIP-Seq

Researchers present a low-cost, efficient, simultaneous indexing and tagmentation-based ChIP-seq (itChIP-seq) method, compatible with both low cellular input and single cells for profiling chromatin states. itChIP combined chromatin opening, simultaneous cellular indexing and chromatin tagmentation within a single tube, enabling the processing of samples from tens of single cells to, more commonly, thousands of single cells per assay. [Nat Cell Biol] Abstract

CaMKII-δ9 Promotes Cardiomyopathy through Disrupting UBE2T-Dependent DNA Repair

Scientists showed that Ca²⁺/calmodulin-dependent kinase II (CaMKII)-δ9 potently promoted cardiomyocyte death, cardiomyopathy and heart failure by disrupting cardiomyocyte genome stability. Mechanistically, CaMKII-δ9, but not the previously well-studied CaMKII-δ2 and CaMKII-δ3, targeted the ubiquitin-conjugating enzyme E2T (UBE2T) for phosphorylation and degradation, disrupting UBE2T-dependent DNA repair and leading to the accumulation of DNA damage and genome instability. [Nat Cell Biol] Abstract

Severe Cardiac Dysfunction and Death Caused by ARVC Type 5 Is Improved by Inhibition of GSK3β

Mutant TMEM43 caused cardiomyocyte death and severe fibro-fatty replacement. The authors also demonstrated that TMEM43 localized at the nuclear membrane and interacted with emerin and β-actin. [Circulation] Abstract | Press Release

Disruption of Cardiac Thin Filament Assembly Arising from a Mutation in LMOD2: A Novel Mechanism of Neonatal Dilated Cardiomyopathy

Leiomodin 2 (Lmod2)-null mice had severe early-onset Duchenne muscular dystrophy and died before weaning. An infant patient’s explanted heart showed extraordinarily short thin filaments with isolated cardiomyocytes displaying a large reduction in maximum calcium-activated force production. [Sci Adv] Full Article

Sema3a-Nrp1 Signaling Mediates Fast-Twitch Myofiber Specificity of Tw2⁺ Cells

Through RNA sequencing and immunofluorescence, researchers identified the membrane receptor, Nrp1, as a marker of Tw2⁺ cells but not Pax7⁺ cells. They also found that Sema3a, a chemorepellent ligand for Nrp1, was expressed by type I and IIa myofibers but not IIb myofibers. [Dev Cell] Full Article | Graphical Abstract

Mechanical Forces Regulate Cardiomyocyte Myofilament Maturation via the VCL-SSH1-CFL Axis

The authors showed that the forces of the contracting heart regulated the localization and activation of the cytoskeletal protein vinculin (VCL), which they found to be essential for myofilament maturation. To further analyze the role of VCL in this process, they examined its interactome in contracting versus non-contracting cardiomyocytes and, in addition to several known interactors, including actin regulators, identified the slingshot protein phosphatase SSH1. [Dev Cell] Full Article | Graphical Abstract

Identification and Characterization of a Transcribed Distal Enhancer Involved in Cardiac Kcnh2 Regulation

Knockdown of Kcnh2‘s ncRNA transcript resulted in reduced expression of Kcnh2b and two neighboring mRNAs, Nos3 and Abcb8, in vitro. Genomic deletion of the enhancer, including the ncRNA transcription start site, from the mouse genome caused a modest downregulation of both Kcnh2a and Kcnh2b in the ventricles. [Cell Rep] Full Article | Graphical Abstract

Human iPSC Modeling of a Familial Form of Atrial Fibrillation Reveals a Gain of Function of I_f and I_CaL in Patient-Derived Cardiomyocytes

Electrophysiological characterization of patient-derived cardiomyocytes (CMs) revealed that they had higher beating rates compared to control CMs. The analysis showed an increased contribution of the I_f and I_CaL currents. No differences were observed in the repolarizing current I_Kr and in the sarcoplasmic reticulum calcium handling. [Cardiovasc Res] Abstract | Full Article | Graphical Abstract

SKELETAL MUSCLE CELLS

Oral Glutamine Supplementation Attenuate Inflammation and Oxidative Stress-Mediated Skeletal Muscle Protein Content Degradation in Immobilized Rats: Role of 70 kDa Heat Shock Protein

Relative to controls, glutamine (GLN) plus alanine (ALA), and L-alanyl-l-glutamine (DIP) baselines, hindlimb immobilization (IMOB) group rats presented significant myofibrillar protein content loss and, reduced plasma and muscle GLN concentration, which was restored in both GLN plus ALA-IMOB and DIP-IMOB animals. [Free Radic Biol Med] Abstract | Graphical Abstract

SMOOTH MUSCLE CELLS

MicroRNA-92a/Sp1/MyoD Axis Regulates Hypoxic Stimulation of Myogenic-Lineage Differentiation in Mouse Embryonic Stem Cells

Scientists found that hypoxia-primed embryoid bodies efficiently differentiated into the myogenic lineage, resulting in the induction of the myogenic marker, MyoD, which was not mediated by HIF1α or HIF2α, but rather by Sp1 induction and binding to the MyoD promoter. Knock-down of Sp1 in hypoxia-primed embryoid bodies abrogated hypoxia-induced MyoD expression and myogenic differentiation. [Mol Ther] Abstract

ALDH1A3 Regulations of Matricellular Proteins Promote Vascular Smooth Muscle Cell Proliferation

The expression of ALDH1A3, but not that of 18 other isoforms of the ALDH family, was substantially increased in cytokine-stimulated vascular smooth muscle cells (VSMCs). While PDGF(BB) stimulated VSMC total ALDH activity and proliferation, ALDH1A3 silencing abolished this effect. [iScience] Full Article | Graphical Abstract

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Human Pluripotent Stem Cell-Derived Cardiovascular Cells: From Developmental Biology to Therapeutic Applications

The authors review the state of the field in generating and maturing cardiovascular cells from human pluripotent stem cells based on their fundamental understanding of heart development. They then highlight their applications for studying human heart development, modeling disease-performing drug screening, and cell replacement therapy. [Cell Stem Cell] Abstract

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

Applied Therapeutics Announces Initiation of Phase III Registrational Trial of AT-001 in Diabetic Cardiomyopathy (ARISE-HF)

Applied Therapeutics Inc. announced the initiation of a Phase III registrational trial for AT-001, a novel, potent and selective aldose reductase inhibitor, in diabetic cardiomyopathy (DbCM). The study, called ARISE-HF, will investigate AT-001’s ability to improve or prevent the decline of functional capacity in patients with DbCM at high risk of progression to overt heart failure. [Applied Therapeutics Inc.] Press Release

Esperion Completes Patient Enrollment in the Global CLEAR Cardiovascular Outcomes Trial for Bempedoic Acid

Esperion announced the completion of patient enrollment in the CLEAR Cardiovascular Outcomes Trial. The trial is designed to evaluate whether treatment with bempedoic acid reduces the risk of cardiovascular events in patients with statin intolerance who have cardiovascular disease or are at high risk for cardiovascular disease. [Esperiod (GlobeNewswire, Inc.)] Press Release

Muscular Dystrophy Association Awards 25 Grants Totaling More than $6.6 Million for Neuromuscular Disease Research

The Muscular Dystrophy Association (MDA) announced the awarding of 25 new MDA grants totaling more than $6.6 million toward research focused on a variety of neuromuscular diseases, including amyotrophic lateral sclerosis, Charcot-Marie-Tooth disease, congenital muscular dystrophy, Duchenne muscular dystrophy, facioscapulohumeral muscular dystrophy, Friedreich’s ataxia, inclusion body myositis, limb-girdle muscular dystrophy, mitochondrial myopathy, myotonic dystrophy, spinal-bulbar muscular atrophy, and spinal muscular atrophy. [The Muscular Dystrophy Association] Press Release

Groundbreaking U of M Medical School Muscle Regeneration Research Receives Nearly $1 Million Grant

The University of Minnesota (U of M) Medical School is feveloping a cell-based therapy for Duchenne muscular dystrophy, and now its team of researchers leading this work has been awarded a $945 thousand grant from Duchenne UK to catalyze advancement of current preclinical discoveries. [The University of Minnesota] Press Release

Reeling from Scandal, Novartis Vows to Voluntarily Release Info on Manipulated Data in the Future

Seeking to appease angry regulators, Novartis committed to notifying the Food and Drug Administration within five business days of learning of any “credible allegation” in which manipulated data may affect a pending marketing application before the agency or regulators in other countries. [STAT News] Editorial

US Funding Scramble Leaves Science Agencies in Limbo

The US Congress has a busy few weeks in store. When lawmakers return from their summer break on 9 September, they’ll have just three weeks to hammer out a 2020 spending deal – and funding for the National Institutes of Health, National Science Foundation and other key science agencies is on the line. [Nature News] Editorial

Animal Registries Aim to Reduce Bias

Registries ask researchers to detail their hypotheses, experimental strategy and analytical plans before studies begin. The intention is to prevent teams from simply cherry-picking significant or desirable findings and to supply the scientific community with a way of learning about experiments that would otherwise go unpublished. [Nature News] Editorial

NEW Stromal Cells in Immunity and Disease
February 19-23, 2020
Victoria, British Columbia, Canada

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NEW Senior Scientist – Small Molecule Therapeutics (Almac Group)

Scientific Communications Coordinator (STEMCELL Technologies Inc.)

Postdoctoral Researcher – Molecular Mechanisms of Heart Failure (Boston University)

Postdoctoral Researcher – Ion Channels in Vascular Smooth Muscle (The University of Tennessee)

Assistant Professor – Applied Cardiovascular Physiology (York University)

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

Postdoctoral Fellow – Cardiovascular Physiology (University of California, San Diego)

Tenure-Track Faculty Position – Integrative Biology and Physiology (University of California, Los Angeles)

Associate Scientist – Drug Discovery Program (Casma Therapeutics)

Research Scientist – Cellular Electrophysiology (Duke University)

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