Muscle Cell News Volume 4.26 | Jul 29 2019

TOP STORY

The Human- and Smooth Muscle Cell-Enriched lncRNA SMILR Promotes Proliferation by Regulating Mitotic CENPF mRNA and Drives Cell-Cycle Progression Which Can Be Targeted to Limit Vascular Remodeling

Investigators used deep RNA-sequencing of human saphenous vein smooth muscle cells stimulated with IL1α and PDGF-BB with SMILR-knockdown or -overexpression to identify SMILR regulated genes. This revealed a SMILR-dependent network essential for cell-cycle progression. [Circ Res] Abstract

(Ranked by impact factor of the journal)

CARDIAC MUSCLE CELLS

PDGFR-β Signaling Regulates Cardiomyocyte Proliferation and Myocardial Regeneration

Employing RNA sequencing, researchers showed that the enhancer of zeste homolog 2 (Ezh2) could be upregulated by platelet-derived growth factor receptor (PDGFR)-β signaling in primary cardiomyocytes. Conditional knockout of Ezh2 blocked cardiomyocyte proliferation and H3K27me3 modification during neonatal heart regeneration with Ink4a/Arf upregulation, even in mice with myocyte-specific conditional activation of PDGFR-β. [Cell Rep] Full Article | Graphical Abstract

Continuous WNT Control Enables Advanced hPSC Cardiac Processing and Prognostic Surface Marker Identification in Chemically Defined Suspension Culture

The feasibility of suspension culture based human pluripotent stem cell-derived cardiomyocyte (hPSC-CM) production in low-cost, xeno-free media compatible with good manufacturing practice standards was shown. Applying stirred tank bioreactor systems at increasing dimensions, scientists’ advanced protocol enabled routine production of about 1 million hPSC-CMs/mL, yielding ~1.3 × 108 CM in 150 mL and ~4.0 × 108 CMs in 350–500 mL process scale at >90% lineage purity. [Stem Cell Reports] Full Article | Graphical Abstract

Divergent Off-Target Effects of RSK N-Terminal and C-Terminal Kinase Inhibitors in Cardiac Myocytes

The ATP competitive N-terminal kinase domain-targeting compounds D1870 and SL0101 and the allosteric C-terminal kinase domain-targeting FMK were evaluated regarding their ability to modulate cardiac myocyte protein phosphorylation. Exposure to D1870 and SL0101 significantly enhanced phospholamban Ser16 and cardiac troponin I Ser22/23 phosphorylation in response to D1870 and SL0101 upon exposure to phenylephrine that activated P90 ribosomal S6 kinases (RSK). [Cell Signal] Abstract

Clinical Trial in a Dish: Personalized Stem Cell Derived Cardiomyocyte Assay Compared to Clinical Trial Results for Two QT Prolonging Drugs

Induced pluripotent stem cell-derived cardiomyocytes were generated from subjects that had 15 time-matched plasma drug concentration and ECG measurements. Their drug-concentration-dependent QT prolongation response from the clinic was compared to in vitro drug-concentration-dependent APD prolongation response to the same two hERG blocking drugs, dofetilide and moxifloxacin. [Clin Transl Sci] Abstract | Full Article

SKELETAL MUSCLE CELLS

Core Transcription Factors Promote Induction of PAX3-Positive Skeletal Muscle Stem Cells

The authors report that four transcription factors, HEYL, KLF4, MYOD, and PAX3, selected by comprehensive screening of different adult skeletal muscle stem cells (MuSC) populations, enhanced the derivation of PAX3-positive myogenic progenitors from fibroblasts and human induced pluripotent stem cells, using medium that promoted the formation of presomitic mesoderm. These induced PAX3-positive cells contributed efficiently to the repair of Duchenne muscular dystrophy-damaged myofibers and also reconstituted the MuSC population. [Stem Cell Reports] Full Article

miR-449a Regulates Insulin Signalling by Targeting the Notch Ligand, Jag1 in Skeletal Muscle Cells

Predicted targets of miR-449a were extracted using online available target prediction tools. Differentiated C2C12 cells were transfected with the miR-449a mimic and/or its inhibitor and the levels of the target mRNA and protein was evaluated by qRT-PCR and Western Blot analysis. [Cell Commun Signal] Full Article

SMOOTH MUSCLE CELLS

p116^Rip Promotes Myosin Phosphatase Activity in Airway Smooth Muscle Cells

To elucidate the role of p116^Rip in cellular contractile processes, scientists suppressed the expression of p116^Rip by RNA interference in human airway smooth muscle cells (HASMCs). They found that knockdown of p116^Rip in HASMCs led to increased di-phosphorylated MLC, that was phosphorylation at both Ser19 and Thr18. [J Cell Physiol] Abstract

Activation of KEAP1/NRF2/P62 Signaling Alleviates High Phosphate-Induced Calcification of Vascular Smooth Muscle Cells by Suppressing Reactive Oxygen Species Production

Researchers investigated the possible involvement of the Kelch-like ECH-associated protein 1 (KEAP1)/NRF2/P62 -mediated antioxidant pathway in vascular calcification induced by high inorganic phosphate (Pi) levels. Exposure of vascular smooth muscle cells to high Pi concentrations promoted the accumulation of reactive oxygen species and the nuclear translocation of NRF2, along with an increase in P62 levels and a decrease in KEAP1 levels. [Sci Rep] Full Article

Knockdown of TRIM28 Inhibits PDGF-BB-Induced Vascular Smooth Muscle Cell Proliferation and Migration

The authors investigated the effects of tripartite motif-containing 28 (TRIM28) on the phenotypic switching of human aortic smooth muscle cells (HASMCs), which is considered as a fundamental event during the development of atherosclerosis. The results showed that TRIM28 was highly expressed in human atherosclerotic tissues, as well in cultured HASMCs stimulated by platelet-derived growth factor subunit B homodimer. [Chem Biol Interact] Abstract

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Age-Related DNA Methylation Changes: Potential Impact on Skeletal Muscle Aging in Humans

Investigators consider the possible use of the recently developed DNA methylation-based biomarkers of aging called epigenetic clocks in the assessment of physical performance in older individuals. Finally, they discuss limitations and future directions of this field. [Front Physiol] Abstract

Bioprinting Approaches to Engineering Vascularized 3D Cardiac Tissues

The provisioning of a functional vasculature is necessary for maintaining a high cell viability and functionality in engineered cardiac tissues. Several recent studies have shown the ability to generate tissues up to a centimeter scale with a perfusable vascular network. [Curr Cardiol Rep] Abstract

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Novartis Provides Update on Phase III PARAGON-HF Trial in Heart Failure Patients with Preserved Ejection Fraction (HFpEF)

Novartis announced topline results from the global Phase III PARAGON-HF study, investigating the safety and efficacy of sacubitril/valsartan versus the active comparator valsartan in HFpEF patients. The trial narrowly missed statistical significance for its composite primary endpoint of reducing cardiovascular death and total heart failure hospitalizations. [Novartis] Press Release

NIH Awards Contract for Acute Flaccid Myelitis Natural History Study

The National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health (NIH), has awarded the University of Alabama at Birmingham approximately $10 million over five years to study acute flaccid myelitis, a rare but serious condition which causes muscle weakness and paralysis. [National Institutes of Health (EurekaAlert)] Press Release

Medical Journal Editors Expect Authors to Disclose Conflicts of Interest- But Don’t Disclose Their Own

Virtually all top medical journals require authors to disclose potential conflicts of interest, but few- just 12%- apply that same medicine to their own editors by publicly disclosing editors’ financial ties to industry, a study has found. [ScienceMagazine] Editorial

Cuts and Dismissive Remarks Unnerve Mexican Scientists

The initially warm relations between Mexico’s academic community and the country’s new president, Andrés Manuel López Obrador, have decidedly cooled. A package of harsh austerity measures, implemented on 3 May, has had a deep impact on federally funded laboratories and institutes; it includes a 30% cut to fuel for vehicles and office supplies and a 50% cut to international travel funds and payments to contract workers. Scientists say the cuts are a serious threat to the future of Mexican research. [ScienceMagazine] Editorial

UK Prime Minister Boris Johnson’s Hardline Brexit Stance Stokes Fears for Scientists

In his inaugural speech last week, Johnson cited the “extraordinary” UK bioscience sector and pledged to ditch European rules that he says have hampered the development of genetically modified crops. He said the nation should develop its own multibillion-dollar GPS satellite system, presumably a response to the EU plan to eliminate the ability of the U.K. government to tap into a secure signal from the European Galileo GPS system. [ScienceMagazine] Editorial

NEW Cardiovascular and Interventional Radiological Society of Europe (CRISE) 2019
September 7-11, 2019
Barcelona, Spain

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

NEW Scientific Communications Coordinator (STEMCELL Technologies Inc.)

NEW Postdoctoral Fellow – Cardiovascular Physiology (University of California)

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

Postdoctoral Fellow – Cardiovascular Biology (Oklahoma Medical Research Foundation)

Senior Scientist – Gene Therapy in Muscle Cells (Shape Therapeutics)

Associate Scientist – Drug Discovery Program (Casma Therapeutics)

Postdoctoral Fellowship – Molecular Mechanisms of Atrial Fibrillation (Electrophysiology and Heart Modeling Institute)

Postdoctoral Fellow – Cardiovascular Biology (Oklahoma Medical Research Foundation)

Research Scientist – Cellular Electrophysiology (Duke University)

Postdoctoral Researcher – Muscle Atrophy and Metabolism (McGill University)

Postdoctoral Researchers – Cardiovascular Studies (Virginia Tech)

Postdoctoral Fellow – Facioscapulohumeral Muscular Dystrophy Research (Pfizer)

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