Muscle Cell News Volume 1.36 | Dec 12 2016

TOP STORY

Nucleoside Diphosphate Kinase-C Suppresses cAMP Formation in Human Heart Failure

Scientists investigated the potential role of nucleoside diphosphate kinases (NDPK)-C in cardiac cAMP formation and contractility. Their findings identified NDPK-C as an essential requirement for both the interaction between NDPK isoforms and with G proteins. [Circulation] Abstract

(Ranked by impact factor of the journal)

CARDIAC MUSCLE CELLS

ATF6 Decreases Myocardial Ischemia/Reperfusion Damage and Links ER Stress and Oxidative Stress Signaling Pathways in the Heart

Investigators examined the effects of blocking the ATF6-mediated ER stress response on ischemia/reperfusion (I/R) in cardiac myocytes and mouse hearts. ATF6 serves as a previously unappreciated link between the ER stress and oxidative stress gene programs, supporting a novel mechanism by which ATF6 decreases myocardial I/R damage. [Circ Res] Abstract

Electrotonic Coupling of Excitable and Nonexcitable Cells in the Heart Revealed by Optogenetics

Researchers used genetically encoded voltage-sensitive fluorescent protein 2.3 (VSFP2.3) to monitor transmembrane potential in either myocytes or nonmyocytes of murine hearts. They showed that VSFP2.3, expressed solely in nonmyocytes, can report cardiomyocyte AP-like signals at the border of healed cryoinjuries. [Proc Natl Acad Sci USA] Full Article

In Vivo Visualization of Cardiomyocyte Apicobasal Polarity Reveals Epithelial to Mesenchymal-like Transition during Cardiac Trabeculation

To elucidate how cardiomyocyte shape changes are regulated during cardiac trabeculation, investigators engineered transgenes to label their apical and basolateral membranes. Using these tools, they observed that compact-layer cardiomyocytes are clearly polarized while delaminating cardiomyocytes have lost their polarity. [Cell Rep] Full Article | Graphical Abstract

Tissue-Engineered 3-Dimensional (3D) Microenvironment Enhances the Direct Reprogramming of Fibroblasts into Cardiomyocytes by MicroRNAs

Researchers reported that a 3D hydrogel environment enhanced miR combo reprogramming of neonatal cardiac and tail-tip fibroblasts. This was associated with significantly increased MMPs expression in 3D versus two-dimensional cultured cells, while pharmacological inhibition of MMPs blocked the effect of the 3D culture on enhanced miR combo mediated reprogramming. They conclude that 3D tissue-engineered environment can enhance the direct reprogramming of fibroblasts to cardiomyocytes via a MMP-dependent mechanism. [Sci Rep] Full Article

SKELETAL MUSCLE CELLS

BRAF Activates PAX3 to Control Muscle Precursor Cell Migration during Forelimb Muscle Development

Migration of skeletal muscle precursor cells is a key step during limb muscle development and depends on the activity of PAX3 and MET. Scientists demonstrated that BRAF serves a crucial function in formation of limb skeletal muscles during mouse embryogenesis downstream of MET and acts as a potent inducer of myoblast cell migration. [eLife] Full Article

Widespread Control of Calcium Signaling by a Family of SERCA-Inhibiting Micropeptides

Researchers identified two transmembrane micropeptides, endoregulin (ELN) and another-regulin (ALN), that share key amino acids with their muscle-specific counterparts and function as direct inhibitors of sarco/endoplasmic reticulum Ca²⁺ ATPase (SERCA) pump activity. The distribution of transcripts encoding ELN and ALN mirrored that of SERCA isoform-encoding transcripts in nonmuscle cell types. Their findings identified additional members of the SERCA-inhibitory micropeptide family, revealing a conserved mechanism for the control of intracellular Ca²⁺ dynamics in both muscle and nonmuscle cell types. [Sci Signal] Abstract

Progressive Muscle Cell Delivery as a Solution for Volumetric Muscle Defect Repair

Scientists proposed an effective cell delivery system utilizing appropriate vascularization at the site of cell implantation that results in volumetric and functional tissue reconstruction. Their method of multiple cell injections in a progressive manner yielded improved cell survival and formed volumetric muscle tissues in an ectopic muscle site. Their strategy supported the reconstruction of functional skeletal muscle tissue in a rodent volumetric muscle loss injury model. [Sci Rep] Full Article

The Maintenance Ability and Ca²⁺ Availability of Skeletal Muscle Are Enhanced by Sildenafil

The authors examined the effects of sildenafil on skeletal muscle at the cellular level using mouse primary skeletal myoblasts (the proliferative form of skeletal muscle stem cells) and myotubes, along with single-cell Ca²⁺ imaging experiments and cellular and biochemical studies. The proliferation of skeletal myoblasts was enhanced by sildenafil in a dose-independent manner. [Exp Mol Med] Full Article

SMOOTH MUSCLE CELLS

SHP-1 Activation Inhibits Vascular Smooth Muscle Cell Proliferation and Intimal Hyperplasia in a Rodent Model of Insulin Resistance and Diabetes

Accelerated migration and proliferation of vascular smooth muscle cells (VSMCs) enhances arterial restenosis after angioplasty in insulin resistance and diabetes. Elevation of Src homology 2-containing protein tyrosine phosphatase 1 (SHP-1) induces apoptosis in the microvasculature. Scientists modulated SHP-1 expression using a transgenic mouse that overexpresses SHP-1 in VSMCs (Shp-1-Tg). SHP-1 agonists were also employed to study the molecular mechanisms underlying the regulation of SHP-1 by oxidized lipids. [Diabetologia] Full Article

TNAP Stimulates Vascular Smooth Muscle Cell Trans-Differentiation into Chondrocytes through Calcium Deposition and BMP-2 Activation: Possible Implication in Atherosclerotic Plaque Stability

The authors’ objective was to determine the role of tissue-nonspecific alkaline phosphatase (TNAP) in trans-differentiation of vascular smooth muscle cells (VSMCs) and calcification. In rodent MOVAS and A7R5 VSMCs, addition of exogenous alkaline phosphatase or TNAP overexpression was sufficient to stimulate the expression of several chondrocyte markers and induce mineralization. [Biochim Biophys Acta] Abstract

Inflammatory Processes in Cardiovascular Disease: A Route to Targeted Therapies

The authors consider the roles of inflammatory processes in the related pathologies of atherosclerosis and acute myocardial infarction, by providing an evaluation of the known and emerging inflammatory pathways. [Nat Rev Cardiol] Abstract

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

Cedars-Sinai to Expand Evaluation of Cardiac Cell Therapy after Winning $7.3 Million California Institute for Regenerative Medicine Grant

Researchers from the Cedars-Sinai Heart Institute and the Cedars-Sinai Department of Medicine are expanding their ongoing evaluation of a novel cell-based therapeutic candidate into the area of pulmonary arterial hypertension. This work will be supported by a recently awarded $7.3 million grant from the California Institute for Regenerative Medicine. [Cedars-Sinai] Press Release

Tenaya Therapeutics Launches with the Goal of Curing Heart Disease

A new biopharmaceutical company, Tenaya Therapeutics Inc., will build on discoveries in cardiovascular disease research made at the Gladstone Institutes, concentrating on regenerative medicine and drug discovery for heart failure. A $50 million investment will push basic science discoveries from Gladstone toward cures for heart disease. [Gladstone Institutes] Press Release

Bayer and Versant Ventures join Forces to Launch Stem Cell Therapy Company BlueRock Therapeutics with USD 225 Million Series A Financing

Bayer AG and Versant Ventures announced the launch of BlueRock Therapeutics, a next-generation regenerative medicine company that plans to develop best-in-class induced pluripotent stem cell therapies to cure a range of diseases using an industry-leading platform. One of BlueRock Therapeutics’ initial programs is to regenerate heart muscle in patients who have had a heart attack or are suffering from chronic heart failure. [Bayer Inc.] Press Release

Renova Therapeutics Secures Novel AAV Vector License for Use in Metabolic and Cardiovascular Gene Therapy Development

Renova^™ Therapeutics announced that it has obtained a nonexclusive license for a novel adeno-associated virus (AAV) vector developed in the laboratory of professor Mark Kay, M.D., Ph.D., at Stanford University. The company plans to use this vector in development of its paracrine gene therapy product pipeline. [Renova Therapeutics^™] Press Release

Brexit by the Numbers: The Fear of Brain Drain

British universities fear losing large swathes of their research staff as the country faces up to Brexit, the split with the European Union. More than 31,000 academics at UK universities are non-British EU citizens, and so may lose their rights to live in the United Kingdom after Brexit. [Nature Trend Watch] Editorial

Italian Scientists Won’t Miss Departing Prime Minister Matteo Renzi

Italian politics is in turmoil after the resignation of Prime Minister Matteo Renzi — but researchers say that they are not particularly sad to see him go. In his almost three years in charge, Renzi promised improvements for universities and science but failed to raise the status of research in the country, according to scientists who complain that he also directly interfered in academic affairs. [Nature News] Editorial

NEW World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases
March 23-26, 2017
Florence, Italy

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

NEW Scientist(s) – Various Biological Research Areas (Sanofi)

Postdoctoral Fellow – Ion Channel Signaling and Metabolism (University of Iowa Carver College of Medicine)

Postdoctoral Researcher – Cardiovascular Research (Oslo University Hospital)

Postdoctoral Research Scientist – Cardiovascular Research (Columbia University Medical Center)

Postdoctoral Associate – Muscle Cell Biology (Sanford Burnham Prebys Medical Discovery Institute)

Western Research Chair – Musculoskeletal Health (Western University Canada)

PhD – Neuromuscular and Cardiovascular Cell Biology (Max-Delbruck Center for Molecular Medicine)

Postdoctoral Associate – Integrative Biology & Physiology (University of Minnesota)

Assistant Professor – Biomedical Engineering (University of South Dakota)

Postdoctoral Fellow – Stem Cells & Cartilage Development/Disease (Boston Children’s Hospital and Harvard Medical School)

Staff Scientist/Research Assistant II – Musculoskeletal Tissue Development (Boston Children’s Hospital and Harvard Medical School)

National Field Product Service Specialist – (Cook MyoSite)

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