Muscle Cell News Volume 4.17 | May 13 2019

TOP STORY

Cardiac Reprogramming Factors Synergistically Activate Genome-Wide Cardiogenic Stage-Specific Enhancers

Researchers performed genome-wide analyses of cardiogenic transcription factors (TFs) binding and enhancer profiling during cardiac reprogramming. They found that the TFs synergistically activated enhancers highlighted by Mef2c binding sites and that Hand2 and Akt1 coordinately recruited other TFs to enhancer elements. Intriguingly, these enhancer landscapes collectively resembled patterns of enhancer activation during embryonic cardiogenesis. [Cell Stem Cell] Full Article | Graphical Abstract

(Ranked by impact factor of the journal)

CARDIAC MUSCLE CELLS

The Immunoproteasome Catalytic β5i Subunit Regulates Cardiac Hypertrophy by Targeting the Autophagy Protein ATG5 for Degradation

Investigators found that the expression and activity of immunoproteasome catalytic subunit β5i were significantly up-regulated in angiotensin II-treated cardiomyocytes and in the hypertrophic hearts. Knockout of β5i in cardiomyocytes and mice markedly attenuated the hypertrophic response, and this effect was aggravated by β5i overexpression in cardiomyocytes and transgenic mice. [Sci Adv] Full Article

Activation of PASK by mTORC1 Is Required for the Onset of the Terminal Differentiation Program

The authors identified Per-Arnt-Sim domain kinase as a downstream phosphorylation (PASK) target of mTORC1 in muscle stem cells during differentiation. They showed that the PASK phosphorylated Wdr5 to stimulate muscle stem cell differentiation by epigenetically activating the myogenin promoter. [Proc Natl Acad Sci USA] Abstract

Adaptation of Human iPSC-Derived Cardiomyocytes to Tyrosine Kinase Inhibitors Reduces Acute Cardiotoxicity via Metabolic Reprogramming

Scientists undertook a systems-level analysis of human cardiomyocytes (CMs) exposed to four tyrosine kinase inhibitors. CMs differentiated from human induced pluripotent stem cells (iPSCs) were exposed to sunitinib, sorafenib, lapatinib, or erlotinib, and responses were assessed by functional assays, microscopy, RNA sequencing, and mass spectrometry. [Cell Syst] Full Article

Myocardial Differentiation Is Dependent Upon Endocardial Signaling during Early Cardiogenesis In Vitro

The authors generated an in vitro, endocardial-specific ablation model using the diphtheria toxin receptor under the regulatory elements of the Nfatc1 genomic locus (NFATc1-DTR). Early treatment of NFATc1-DTR mouse embryoid bodies with diphtheria toxin efficiently ablated endocardial cells, which significantly attenuated the percentage of beating EBs in culture and expression of early and late myocardial differentiation markers. [Development] Abstract

Mitochondrial Protein 18 Is a Positive Apoptotic Regulator in Cardiomyocytes under Oxidative Stress

Scientists aimed to detect the role of Mtp18 in H₂O₂-induced mitochondrial fission and apoptosis in cardiomyocytes. They studied the effect of Mtp18 in cardiomyocytes by modulating its expression with lentiviral construct of Mtp18-shRNA and Mtp18 c-DNA, respectively. [Clin Sci (Lond)] Abstract

MiR-423-5p Inhibition Alleviates Cardiomyocyte Apoptosis and Mitochondrial Dysfunction Caused by Hypoxia/Reoxygenation through Activation of the Wnt/β-Catenin Signaling Pathway via Targeting MYBL2

H9C2 cells were transfected with negative control, miR-423-5p mimic, and inhibitor for 48 hours, followed by exposed to hypoxia/reoxygenation condition. Cell apoptosis rate, caspase 3/7 activities, Bax and cleaved-caspase 3 protein levels were assayed by flow cytometry, Caspase-Glo 3/7 Assay kit, and western blot analysis, respectively. [J Cell Physiol] Abstract

Irisin Exerts a Therapeutic Effect against Myocardial Infarction via Promoting Angiogenesis

Researchers investigated the therapeutic effects of irisin in an acute myocardial infarction (MI) model and its underlying mechanisms. Adult C57BL/6 mice were subjected to ligation of the left anterior descending coronary artery and treated with irisin for two weeks after MI. Cardiac function was assessed using echocardiography. [Acta Pharmacol Sin] Abstract

SKELETAL MUSCLE CELLS

Autophagy Induction in Atrophic Muscle Cells Requires ULK1 Activation by TRIM32 Through Unanchored K63-Linked Polyubiquitin Chains

Investigators showed that TRIM32 was required for the induction of muscle autophagy in atrophic conditions using both in vitro and in vivo mouse models. Trim32 inhibition resulted in a defective autophagy response to muscle atrophy, associated with increased ROS and MuRF1 levels. [Sci Adv] Full Article

Highly Porous Microcarriers for Minimally Invasive In Situ Skeletal Muscle Cell Delivery

Highly open porous microspheres (HOPMs) were fabricated using a microfluidic technique for harboring proliferating skeletal myoblasts and evaluating their feasibility toward cell delivery application in situ. These biocompatible HOPMs with particle sizes of 280–370 µm possessed open pores of 10–80 µm and interconnected paths. [Small] Abstract

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

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

SMOOTH MUSCLE CELLS

lncRNA COPDA1 Promotes Airway Smooth Muscle Cell Proliferation in Chronic Obstructive Pulmonary Disease

Lung tissues were collected from nonsmokers, smokers, or smokers with chronic obstructive pulmonary disease (COPD) for RNA-seq. Bioinformatics analysis and cell experiments were employed to define the function of COPDA1 and the effects of COPDA1 on intracellular Ca²⁺ concentration and cell proliferation were examined after knockdown or overexpression of COPDA1. [Am J Respir Cell Mol Biol] Abstract

Subscribe to one of our other 19 science newsletters such as Extracellular Matrix News & ESC & iPSC News.

The Role of Reactive Oxygen Species in In Vitro Cardiac Maturation

The authors focus on reactive oxygen species (ROS), signaling molecules that can potentially modulate cardiac maturation. They outline how ROS impacts nearly every aspect associated with cardiac maturation, including contractility, calcium handling, metabolism, and hypertrophy. [Trends Mol Med] Abstract

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

Valadrius Biosciences to Participate at the Upcoming May Conferences

Caladrius Biosciences, Inc. announced that management will participate in two conferences in May, with the following presentations: ‘The Microcirculation: Center of the Cardiovascular Repair Universe’ and ‘Single Administration of CD34 Cell Reverses Cardiovascular Disease: Evidence from >700 patients in randomized clinical trials.’ [Press release from Caladrius Biosciences, Inc. discussing research to be presented at the 16^th International Symposium on Cardiovascular Regeneration and Repair, Madrid, and 2019 World Advanced Therapies & Regenerative Medicine Congress, London] Press Release

Roche Presents Data from the Risdiplam Pivotal FIREFISH and SUNFISH Studies in Spinal Muscular Atrophy

Roche announced new data from the dose-finding Part 1 of the pivotal FIREFISH trial showing infants with Type 1 spinal muscular atrophy achieved key motor milestones after one year of treatment with investigational risdiplam. [Press release from Roche discussing research presented at the 71^st American Academy of Neurology (AAN) Annual Meeting, Philadelphia] Press Release

Sarepta Announces Agreement with Nationwide Children’s Hospital for Rights to Its Gene Therapy Program to Treat Limb-Girdle Muscular Dystrophy Type 2A, the Most Common Form of Limb-Girdle Muscular Dystrophy

Sarepta Therapeutics, Inc. announced it has recently signed an agreement with the Research Institute at Nationwide Children’s Hospital giving Sarepta the exclusive option to a Nationwide Children’s gene therapy candidate, calpain 3, to treat limb-girdle muscular dystrophy type 2A. [Sarepta Therapeutics, Inc.] Press Release

Broad Institute, Harvard Extend CRISPR Human Therapeutics License to Verve Therapeutics

Harvard University and the Broad Institute of MIT and Harvard have issued licenses for key CRISPR-Cas9 and -Cas12a genome editing technology to Verve Therapeutics to enable development of human therapeutic applications against certain cardiovascular targets. [The Broad Institute] Press Release

Agreement Secured by ProtoKinetix to Start Heart Research Product Validation Studies

ProtoKinetix, Inc. announced that the company has secured a partnership agreement with IMPART investigator team Canada at Dalhousie University and has now commenced studies to reveal the benefits of PKX-001 in cardiac metabolism. These studies will determine the efficacy of PKX-001 as a cardioprotectant and will be led by Diabetes Canada Scholar, Dr. Thomas Pulinilkunnil. [ProtoKinetix, Inc. (Business Wire, Inc.)] Press Release

Scholar Rock Announces Initiation of Patient Dosing in Phase II Trial of SRK-015 in Spinal Muscular Atrophy

Scholar Rock Holding Corporation announced the initiation of patient dosing in the Phase II clinical trial of SRK-015, a highly specific inhibitor of myostatin activation, in Type 2 and Type 3 Spinal Muscular Atrophy. All patients will receive SRK-015 once every four weeks either as a monotherapy or in conjunction with an approved SMN upregulator therapy. [Scholar Rock Holding Corporation] Press Release

FDA Approves New Treatments for Heart Disease Caused by a Serious Rare Disease, Transthyretin Mediated Amyloidosis

The FDA approved Vyndaqel and Vyndama capsules for the treatment of the heart disease caused by transthyretin mediated amyloidosis (ATTR-CM) in adults. These are the first FDA-approved treatments for ATTR-CM. Vyndaqel and Vyndamax have the same active moiety, tafamidis, but they are not substitutable on a milligram to milligram basis and their recommended doses differ. [The Food and Drug Administration] Press Release

Academics Raise Concerns About Predatory Journals on PubMed

The National Library of Medicine has quality control procedures in place, but some researchers believe additional scrutiny is necessary. [The Scientist] Editorial

Brazilian Biomedical Science Faces Reproducibility Test

An ambitious project to test the reproducibility of biomedical experiments by Brazilian scientists is about to get under way. The Brazilian Reproducibility Initiative was launched last year by researchers at the Federal University of Rio de Janeiro. Now, the first wave of reproducibility testing is set to begin in August, with help from more than 60 laboratories scattered over 43 Brazilian research centers. [Nature News] Editorial

US Lawmakers Propose Plan to Reduce Primate Research at National Institutes of Health

The US National Institutes of Health (NIH) would be required to reduce its use of non-human primates in research, under a spending bill approved on 8 May by a committee in the US House of Representatives. The bill would direct the NIH “to accelerate efforts to reduce and replace the use of nonhuman primates with alternative research models” in its laboratories. [Nature News] Editorial

NEW The 2019 Canadian Cardiovascular Congress
October 24-27, 2019
Montreal, Quebec, Canada

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

NEW 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)

Postdoctoral Researcher – Proliferative Responses in Cardiac Disease (University of Cambridge)

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)

Postdoctoral Scholar – Cardiovascular Genomics (Stanford Medicine)

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)

Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.

Have we missed an important article or publication in Muscle Cell News? Click here to submit!

Comments or suggestions? Submit your feedback here.