Muscle Cell News Volume 4.35 | Oct 21 2019

TOP STORY

Cronos Titin Is Expressed in Human Cardiomyocytes and Necessary for Normal Sarcomere Function

To investigate the function of titin in human cardiomyocytes (CMs), researchers used CRISPR/Cas9 to generate homozygous truncations in the Z-disk and A-band regions of the TTN gene in human induced pluripotent stem cells. The resulting CMs were characterized using immunostaining, engineered heart tissue mechanical measurements, and single cell force and calcium measurements. [Circulation] Abstract

(Ranked by impact factor of the journal)

CARDIAC MUSCLE CELLS

Control of Cytokinesis by β-Adrenergic Receptors Indicates an Approach for Regulating Cardiomyocyte Endowment

Investigators used single-cell transcriptional profiling to discover that the underlying mechanism of cytokinesis failure was repression of the cytokinesis gene ECT2, downstream of β-adrenergic receptors (β-ARs). Inactivation of the β-AR genes and administration of the β-blocker propranolol increased cardiomyocyte division in neonatal mice, which increased the number of cardiomyocytes and conferred benefit after myocardial infarction in adults. [Sci Transl Med] Full Article

TFPa/HADHA Is Required for Fatty Acid Beta-Oxidation and Cardiolipin Re-Modeling in Human Cardiomyocytes

The authors report that matured hydratase subunit A (HADHA)ll mutant cardiomyocytes treated with an endogenous mixture of fatty acids manifested the disease phenotype: defective calcium dynamics and repolarization kinetics which resulted in a pro-arrhythmic state. Single cell RNA-seq revealed a cardiomyocyte developmental intermediate, based on metabolic gene expression. [Nat Commun] Full Article

Living Myofibroblast-Silicon Composites for Probing Electrical Coupling in Cardiac Systems

Scientists hybridized cardiac myofibroblasts with silicon nanowires and used these engineered hybrids to synchronize the electrical activity of cardiomyocytes, studying heterocellular bioelectric coupling in vitro. They injected the engineered myofibroblasts into heart tissues and showed their ability to seamlessly integrate into contractile tissues in vivo. [Proc Natl Acad Sci USA] Abstract

Stoichiometric Optimization of Gata4, Hand2, Mef2c, and Tbx5 Expression for Contractile Cardiomyocyte Reprogramming

Researchers showed that controlled stoichiometric expression of Gata4, Hand2, Mef2c, and Tbx5 significantly enhanced contractile cardiomyocyte reprogramming over previously defined stoichiometric expression of GMT or uncontrolled expression of GHMT. [Sci Rep] Full Article

miR-499 Responsive Lethal Construct for Removal of Human Embryonic Stem Cells after Cardiac Differentiation

Insertion of miR-499 target sites in the construct enabled investigators to enrich human embryonic stem cell-derived cardiomyocytes in culture. A deterministic non-linear model was developed and validated with experimental data, to predict the outcome for each treatment cycle and the number of treatment cycle repetitions required to achieve completely purified cTNT-positive cells. [Sci Rep] Full Article

SKELETAL MUSCLE CELLS

Inhibition of lncRNA XIST Improves Myocardial Ischemic-Reperfusion Injury by Targeting miR-133a through Inhibition of Autophagy and Regulation of SOCS2

H9C2 cells treated by hypoxia/reoxygenation were used to establish in vitro ischemic-reperfusion model. The siRNA for XIST and miR-133 mimics, inhibitor and SOCS2 recombinant plasmids were used to transfect the cells. Cell apoptosis was determined by flow cytometry analysis and cell viability was used for MTT assay. [Mol Ther Nucleic Acids] Abstract | Full Article

Impairment of Mitochondrial Bioenergetics and Permeability Transition Induction Caused by Major Long-Chain Fatty Acids Accumulating in VLCAD Deficiency in Skeletal Muscle as Potential Pathomechanisms of Myopathy

Scientists investigated the effects of cis-5-Tetradecenoic (cis-5) and myristi (Myr) on mitochondrial bioenergetics and Ca²⁺ homeostasis in rat skeletal muscle. cis-5 and Myr decreased ADP-stimulated and CCCP-stimulated (uncoupled) respiration, especially when mitochondria were supported by NADH-linked as compared to FADH2-linked substrates. [Toxicol In Vitro] Abstract

Muscle Tissue Engineering in Fibrous Gelatin: Implications for Meat Analogs

To produce meat analogs, researchers cultured bovine aortic smooth muscle cells and rabbit skeletal muscle myoblasts in gelatin fiber scaffolds, then used immunohistochemical staining to verify that both cell types attached to gelatin fibers and proliferated in scaffold volumes. Short-length gelatin fibers promoted cell aggregation, whereas long fibers promoted aligned muscle tissue formation. [npj Sci Food] Full Article

SMOOTH MUSCLE CELLS

TRIM7 Promotes Proliferation and Migration of Vascular Smooth Muscle Cells in Atherosclerosis Through Activating C-Jun/AP-1

Investigators discovered that TRIM7 expression was robustly induced in platelet-derived growth factor type BB-treated vascular smooth muscle cells (VSMCs) and human atherosclerotic plaques. Functional approaches established that knockdown of TRIM7 inhibited proliferation and migration of VSMCs, as well as arrested the cell cycle at G1-S, thus suppressing atherosclerosis progression. [IUBMB Life] Abstract

Resveratrol Loaded Polyurethane Nanofibrous Scaffold: Viability of Endothelial and Smooth Muscle Cells

The viability of human umbilical vein endothelial cells and smooth muscle cells on resveratrol-loaded scaffolds was evaluated. Findings demonstrated that resveratrol-loaded nanofibers resulted in not only appropriate antithrombotic properties but also formation a monolayer of endothelial cells on the scaffold surface and lower smooth muscle cell growth. [Biomed Mater] Abstract

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Vascularized and Innervated Skeletal Muscle Tissue Engineering

Due to the complex vascular and neural anatomy within skeletal muscle, regeneration of functional vasculature and nerves is vital for muscle recovery following volumetric muscle loss (VML) injuries. The authors summarize the current state of the field of skeletal muscle tissue engineering using 3D constructs for VML treatment with a focus on studies that have promoted vascular and neural regeneration within the muscle tissue post-VML. [Adv Healthc Mater] Abstract

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OPKO and Pfizer Announce Positive Phase III Top-Line Results for Somatrogon, an Investigational Long-Acting Human Growth Hormone to Treat Children with Growth Hormone Deficiency

OPKO Health Inc. and Pfizer Inc. announced today that the global Phase III trial evaluating somatrogon dosed once-weekly in pre-pubertal children with growth hormone deficiency met its primary endpoint of non-inferiority to daily GENOTROPIN^® for injection, as measured by annual height velocity at 12 months. [OPKO Health Inc.] Press Release

Nonprofit CureDuchenne Launches Biobank to Fuel Research for Duchenne Muscular Dystrophy

CureDuchenne, a global leader in research, patient care, and innovation in improving and extending the lives of those living with Duchenne muscular dystrophy (Duchenne), announced it has initiated the development of a biobank for Duchenne. The CureDuchenne Biobank is dedicated to empowering Duchenne research and the search for a cure for Duchenne that is independent and accessible to all researchers. [CureDuchenne] Press Release

AstraZeneca HealthCare Foundation Awards $775,000 to 11 Innovative Heart Health Programs & Announces Open Call for Applications

Eleven innovative, communit–based programs are helping improve the heart health of people in the areas they serve thanks in part to grants totaling $775,000 from the AstraZeneca HealthCare Foundation’s Connections for Cardiovascular HealthSM program. Many of these organizations also are sharing their cumulative lessons learned and approaches to preventing and controlling cardiovascular disease so that other organizations throughout the country may benefit. [AstraZeneca HealthCare Foundation] Press Release

Brexit Hits UK Science Funding and Workforce

The first figures have emerged demonstrating that Brexit uncertainty has adversely affected UK research. They show Britain’s annual share of EU research funding has fallen by nearly a third since 2015. [The BBC] Editorial

Scientific Integrity Bill Advances in US House with Bipartisan Support

Despite their failure to attract a single Republican co-sponsor, Democrats in Congress have long insisted that a bill to strengthen scientific integrity across US government agencies takes a bipartisan stance and is not a veiled attack on the Trump administration’s attitude toward science. That claim of bipartisanship took a big step forward as the science committee of the US House of Representatives tweaked the bill to satisfy key Republicans on the panel. [ScienceMagazine] Editorial

NEW Linking Cells, the Cytoskeleton and the Nucleus in Mechanobiology, Aging and Disease
June 7-12, 2020
West Dover, Vermont, United States

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NEW Postdoctoral Researcher – Genome Editing in Cardiac Microtissues (The Jackson Laboratory)

NEW Research Scientists – Cardiac and Neuronal Cell Differentiation (Evotec)

Postdoctoral Fellow – Skeletal Muscle (Harvard Medical School)

Scientific Associate – Cardiac Cell Therapy (Avery Therapeutics)

Research Scientist – Metabolic & Muscle Diseases (Regeneron)

Research Scientist – Gene Therapy for Neuromuscular Disorders (Vertex Pharmaceuticals)

Researcher – Skeletal Muscle Mechanics and Energetics (University of California, Riverside)

NEW Postdoctoral Researcher – Skeletal Muscle Aging and Proteostasis (St. Jude Children’s Research Hospital)

Senior Scientist – Small Molecule Therapeutics (Almac Group)

Assistant Professor – Applied Cardiovascular Physiology (York University)

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

Research Scientist – Cellular Electrophysiology (Duke University)

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