Muscle Cell News Volume 4.36 | Oct 28 2019

TOP STORY

HDAC9 Is Implicated in Atherosclerotic Aortic Calcification and Affects Vascular Smooth Muscle Cell Phenotype

Increased expression of HDAC9 in human aortic smooth muscle cells promoted calcification and reduced contractility, while inhibition of HDAC9 in human aortic smooth muscle cells inhibited calcification and enhanced cell contractility. In matrix Gla protein-deficient mice, a model of human vascular calcification, mice lacking HDAC9 had a 40% reduction in aortic calcification and improved survival. [Nat Genet] Abstract

(Ranked by impact factor of the journal)

CARDIAC MUSCLE CELLS

Uncoupling of PARP1 Trapping and Inhibition Using Selective PARP1 Degradation

Scientists designed a series of small molecule PARP degraders. Treatment with one such compound iRucaparib-AP6 results in highly efficient and specific PARP1 degradation. iRucaparib-AP6 blocked the enzymatic activity of PARP1 in vitro, and PARP1-mediated poly-ADP-ribosylation signaling in intact cells. [Nat Chem Biol] Abstract

Adult sox10⁺ Cardiomyocytes Contribute to Myocardial Regeneration in the Zebrafish

Using sox10 genetic fate mapping, researchers identified a subset of pre-existent cardiomyocytes in the adult zebrafish heart with a distinct gene expression profile that expanded after cryoinjury. Genetic ablation of sox10⁺ cardiomyocytes impaired cardiac regeneration, revealing that these cells played a role in heart regeneration. [Cell Rep] Full Article | Graphical Abstract

Canonical Wnt Signaling Promotes Pacemaker Cell Specification of Cardiac Mesodermal Cells Derived from Mouse and Human Embryonic Stem Cells

Omitting an exogenous Wnt inhibitor, which is routinely added to maximize cardiac myocyte yield during differentiation of mouse and human embryonic stem cells, led to increased yield of spontaneously-beating cardiomyocytes with action potential properties similar to those of native sinoatrial node pacemaker cells. The pacemaker phenotype was accompanied by enhanced expression of genes and gene products that mark nodal pacemaker cells such as Hcn4, Tbx18, Tbx3 and Shox2. [Stem Cells] Abstract

Cardiac Pacemaker Cells Generate Cardiomyocytes From Fibroblasts in Long-Term Cultures

Sinoatrial node cells (SANCs) were isolated from adult guinea pig hearts and were cultured at relatively low cell densities. Within a week, a number of fibroblast-like cells were observed to gather around SANCs, and these formed spontaneously beating clusters with cardiomyocyte structures. [Sci Rep] Full Article

SKELETAL MUSCLE CELLS

MicroRNAs Facilitate Skeletal Muscle Maintenance and Metabolic Suppression in Hibernating Brown Bears

Using quantitative reverse transcription PCR, scientists characterized the responses of 36 microRNAs linked with development, metabolism, and regeneration of skeletal muscle, in the vastus lateralis of brown bears comparing winter hibernating and summer active animals. Relative levels of mRNA of selected genes implicated upstream and downstream of the microRNAs were examined. [J Cell Physiol] Abstract

Morphological Evidence for Telocytes as Stromal Cells Supporting Satellite Cell Activation in Eccentric Contraction-Induced Skeletal Muscle Injury

Researchers explored the presence of telocytes and their relationship with satellite cells in an ex vivo model of eccentric contraction (EC)-induced muscle damage. EC-injured muscles showed structural/ultrastructural alterations and changes in electrophysiological sarcolemnic properties. [Sci Rep] Full Article

Dysregulated Cell Signalling and Reduced Satellite Cell Potential in Ageing Muscle

The authors examined the expression of SULF1/SULF2 and members of receptor tyrosine kinase and the Wnt family in skeletal muscle of normal and a mouse model of accelerated ageing. They showed that SULF1/SULF2 and these signaling components, a feature of early muscle development, were barely detectable in early postnatal muscle. [Exp Cell Res] Abstract

SMOOTH MUSCLE CELLS

Differential Estrogen-Receptor Activation Regulates Extracellular Matrix Deposition in Human Airway Smooth Muscle Remodeling via NF-κB Pathway

Investigators evaluated the effect of ER-α vs. ER-β activation on extracellular matrix (ECM) production, deposition, and underlying pathways. Primary human ASM cells isolated from asthmatics and nonasthmatics were treated with E2, an ER-α agonist , and an ER-β agonist with TNF-α or platelet-derived growth factor followed by evaluation of ECM production and deposition. [FASEB J] Abstract

Thymoquinone Suppresses Platelet-Derived Growth Factor-BB-Induced Vascular Smooth Muscle Cell Proliferation, Migration and Neointimal Formation

Scientists systematically examined inhibitory effects of thymoquinone on platelet-derived growth factor-BB-induced proliferation and migration of vascular smooth muscle cells in vitro and neointimal formation in vivo and elucidate the potential mechanisms. Vascular smooth muscle cells were isolated from the aorta in rats. [J Cell Mol Med] Full Article

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Cell Fusion: Merging Membranes and Making Muscle

Recent findings have highlighted the varied protein machinery that drives plasma-membrane merger in different systems, which is characterized by diverse structural and functional elements. The authors highlight the discovery and activities of several key sets of fusion proteins that together offer an evolving perspective on cell membrane fusion. [Trends Cell Biol] Abstract

The Regulatory Role of Myomaker and Myomixer-Myomerger-Minion in Muscle Development and Regeneration

Both Myomaker and Myomixer-Myomerger-Minion have the capacity to directly control the myogenic fusion process. Investigators review and discuss the latest studies related to these two proteins, including the discovery, structure, expression pattern, functions, and regulation of Myomaker and Myomixer-Myomerger-Minion. [Cell Mol Life Sci] Abstract

Stem Cell-Based Therapies for Duchenne Muscular Dystrophy

The cause of Duchenne muscular dystrophy is a mutation in the dystrophin gene, whose encoded protein provides both structural support and cell signaling capabilities. Scientists discuss the existing cell therapy research, especially stem cell-based, which utilize myoblasts, satellite cells, bone marrow cells, mesoangioblasts and CD133⁺ cells. [Exp Neurol] Full Article

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aTyr Pharma Announces Research Collaboration With Boston Children’s Hospital

aTyr Pharma, Inc. announced that the company has entered into a research collaboration with Boston Children’s Hospital. Dr Diane Bielenberg, Assistant Professor in the Department of Surgery at Harvard Medical School and a Research Associate in the Vascular Biology Program at Boston Children’s, will serve as the principal investigator for the collaboration. [aTyr Pharma, Inc.] Press Release

Axcella Enters into Collaboration with CYTOO to Explore Impact of Dysregulated Metabolism on Muscle Physiology

Axcella Health announced a collaboration with CYTOO aimed at informing the development of new AXA Candidates by leveraging CYTOO’s MyoScreenT™muscle-on-a-plate platform. This platform is expected to enable a deeper understanding of how endogenous metabolic modulator compositions influence cellular processes governing the maintenance of muscle mass and function. [Axcella Health] Press Release

MyoKardia Announces Positive MYK-491 Data; Advancing Program Into Targeted Genetic Dilated Cardiomyopathy Population

MyoKardia, Inc. announced positive interim data from the company’s Phase IIa clinical trial of MYK-491 and will advance MYK-491 into a Phase II study in patients with genetic dilated cardiomyopathy. MYK-491 is MyoKardia’s lead activator candidate designed to increase the contractility of the heart with minimal or no effect on myocardial relaxation and compliance by acting directly on the proteins in the heart muscle responsible for contraction. [MyoKardia, Inc.] Press Release

UCL to Phase Out Single-Use Plastics, Including Pipette Tips

University College London made a series of pledges last week to cut down on plastic waste, help mitigate climate change, and make its research and teaching facilities more environmentally sustainable, according to a press release issued on October 16. If all goes to plan, UCL will divest from fossil fuel-producing companies by the end of this year, have one and a half football pitches’ worth of green space on its campus within five years, and offer vegetarian options only through its catering and hospitality services by 2030. [The Scientist] Editorial

Argentine Scientists Rally Behind Favorite in Sunday’s Presidential Election

Thousands of Argentine scientists are hoping the man expected to be the country’s next president will reverse deep cuts to research imposed by the conservative government of President Mauricio Macri. But the first priority for Alberto Fernández, the front-runner in October 27^th‘s election, will almost certainly be Argentina’s crumbling economy. And it’s not clear when- or how effectively- the concerns of scientists will be addressed. [ScienceInsider] Editorial

German University Finds ‘Severe’ Misconduct by Researcher Who Promoted Questionable Cancer Blood Test

A university commission announced this week it had found evidence of “extensive and severe scientific misconduct” by Christof Sohn, director of the women’s clinic at Heidelberg University Hospital in Germany and the lead researcher behind a highly publicized but questionable blood test designed to detect breast cancer. [ScienceInsider] Editorial

NEW FGF Signaling: Understanding Function and Devising Therapeutic Tools
May 10-15, 2020
Tuscany, Italy

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NEW Postdoctoral Researcher – Larngeal Muscle Development (Columbia University)

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

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)

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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