Muscle Cell News Volume 4.28 | Aug 19 2019

TOP STORY

The lncRNA Locus Handsdown Regulates Cardiac Gene Programs and Is Essential for Early Mouse Development

Researchers identified a novel and essential lncRNA locus Handsdown (Hdn), active in early heart cells, and showed by genetic inactivation that it was essential for murine development. Hdn displayed haploinsufficiency for cardiac development as Hdn-heterozygous adult mice exhibited hyperplasia in the right ventricular wall. [Dev Cell] Full Article | Graphical Abstract

(Ranked by impact factor of the journal)

CARDIAC MUSCLE CELLS

Mono- and Multi-Nucleated Ventricular Cardiomyocytes Constitute a Transcriptionally Homogenous Cell Population

Scientists developed an array-based approach for scRNA-seq of rod-shaped multi-nucleated cardiomyocytes from both healthy and hypertrophic hearts. Single-cell transcriptomes of mono- or multi-nucleated cardiomyocytes were highly similar, although a certain degree of variation was noted across both populations. [Basic Res Cardiol] Full Article

Lnc 3215 Suppression Leads to Calcium Overload in Selenium Deficiency-Induced Chicken Heart Lesion via Lnc3215-miR-1594-TNN2 Pathway

Researchers employed Lnc 3215 and TNNT2 knockdown, miR-1594 knockdown and over-expression models in the chicken embryos in vivo, Lnc315, miR-1594 and TNNT2 knockdown and over-expression models in cardiomyocytes in vitro. The dual luciferase reporter assay and real-time quantitative PCR were used to confirm the relationships between miR-1594 and TNNT2, Lnc 3215 and miR-1594 in cardiomyocytes. [Mol Ther Nucleic Acids] Abstract

MLP-Deficient Human Pluripotent Stem Cell Derived Cardiomyocytes Develop Hypertrophic Cardiomyopathy and Heart Failure Phenotypes Due to Abnormal Calcium Handling

The authors generated a knockout muscle LIM protein (MLP)/CSRP3 human embryonic stem cell (hESC) H9 cell line using CRISPR/Cas9 mediated gene disruption. CSRP3 disruption had no impact on the cardiac differentiation of H9 cells and led to confirmed MLP deficiency in hESC-derived cardiomyocytes. [Cell Death Dis] Full Article

Activation of Cardiac AMPK-FGF21 Feed-Forward Loop in Acute Myocardial Infarction: Role of Adrenergic Overdrive and Lipolysis Byproducts

Like AICAR, an activator of AMPK, catecholamines and saturated fatty acids significantly increased fibroblast growth factor 21 (FGF21) production and release by cardiac myocytes via AMPK activation. Recombinant FGF21 induced its own expression as well as members of down-stream targets of AMPK involved in metabolic homeostasis and mitochondrial biogenesis in cardiac myocytes. [Sci Rep] Full Article

SKELETAL MUSCLE CELLS

Molecular Analysis of Muscle Progenitor Cells on Extracellular Matrix Coatings and Hydrogels

Researchers examined whether substrates composed of extracellular matrix proteins, as either coatings or hydrogels, could support expansion of the muscle progenitor cell population whilst maintaining the potency of these cells. The collagen based hydrogels were very pliant and studies demonstrated that stiffer substrates were necessary for in vitro proliferation and differentiation of satellite cells, and the extracellular matrix composition was not significantly important. [Acta Biomater] Abstract

Muscle Satellite Cells and Impaired Late Stage Regeneration in Different Murine Models for Muscular Dystrophies

The authors studied adult muscle of the dystrophic strains: DMD^mdx, Large^myd, DMD^mdx/Large^myd, with variable histopathological alterations. Similar results were observed in the dystrophic models, which maintained normal levels of PAX7 expression, retained the Pax7-positive satellite cell pool, and their proliferation capacity. [Sci Rep] Full Article

A Role for Regulator of G Protein Signaling-12 (RGS12) in the Balance between Myoblast Proliferation and Differentiation

Consistent with a potential role in coordinating myogenic signals, RGS12 was expressed in primary myoblasts; as these cells underwemt differentiation and fusion into myotubes, RGS12 protein abundance was reduced. Myoblasts isolated from mice lacking Rgs12 expression had impaired ability to differentiate into myotubes ex vivo, suggesting that RGS12 may play a role as a modulator/switch for differentiation. [PLoS One] Full Article

SMOOTH MUSCLE CELLS

ApoER2 (Apolipoprotein E Receptor-2) Deficiency Accelerates Smooth Muscle Cell Senescence via Cytokinesis Impairment and Promotes Fibrotic Neointima after Vascular Injury

Vascular smooth muscle cells isolated from apolipoprotein E receptor-2 (apoE)^-/- mice were hyperplastic whereas Lrp8^-/- smooth muscle cells showed reduced proliferation but responded robustly to transforming growth factor-β-induced fibronectin synthesis indicative of a senescence-associated secretory phenotype, which was confirmed by increased β-galactosidase activity, p16^INK4a immunofluorescence, and number of multinucleated cells. [Arterioscler Thromb Vasc Biol] Abstract

Generation of a Purified iPSC-Derived Smooth Muscle-Like Population for Cell Sheet Engineering

Investigators developed murine and human induced pluripotent stem cells (iPSC) lines carrying fluorochrome reporters that identified Acta²⁺/ACTA²⁺ cells as they emerged in vitro in real time during iPSC-directed differentiation. They found that Acta2^hrGFP+ and ACTA2^eGFP+ cells could be sorted to purity and were enriched in markers characteristic of an immature or synthetic smooth muscle cells. [Stem Cell Reports] Full Article | Graphical Abstract

Potential Role of Cartilage Oligomeric Matrix Protein in the Modulation of Pulmonary Arterial Smooth Muscle Superoxide by Hypoxia

Scientists examined if changes in superoxide metabolism could be an important factor in a bovine pulmonary artery (BPA), organoid cultured under hypoxia for 48 hours model. Hypoxis caused a depletion of cartilage oligomeric matrix protein in BPA, but not in bovine coronary arteries. [Am J Physiol Lung Cell Mol Physiol] Abstract

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

Handling Parathormone Receptor Type 1 in Skeletal Diseases: Realities and Expectations of Abaloparatide

The authors address the distinguishing mechanisms of parathyroid hormone-related peptide (PTH1R) activation; the effects of PTH1R stimulation in osteoblast, osteocytes, and chondrocytes; the differences between PTH and abaloparatide actions on PTH1R; potential safety concerns; and future perspectives about abaloparatide use in other musculoskeletal disorders. [Trends Endocrinol Metab] Abstract

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

Fulcrum Therapeutics Announces Initiation of ReDUX4, a Phase IIb Clinical Trial of Losmapimod for FSHD

Fulcrum Therapeutics, Inc. announced it has initiated ReDUX4, a Phase IIb clinical trial of losmapimod in facioscapulohumeral muscular dystrophy (FSHD). The clinical trial is designed to evaluate the efficacy and safety of losmapimod, an investigational selective p38α/β MAPK inhibitor, in addressing the underlying cause of FSHD, a rare, progressive and disabling muscular dystrophy. [Fulcrum Therapeutics, Inc.] Press Release

MyoKardia Launches 2^nd Annual MyoSeeds™ Research Grants Program to Advance Independent Research in Heart Disease

MyoKardia, Inc. announced the launch of the 2^nd Annual MyoSeeds™ Research Grants Program, an initiative to support original, independent research in the biology and underlying mechanisms of cardiomyopathies and precision heart disease treatment. [MyoKardia, Inc.] Press Release

Creating New Muscle by Using Stem Cells

The DMD INSPIRE Major Grant of $945,654 will support the University of Minnesota’s pioneering work on regenerating muscle in Duchenne Muscular Dystrophy (DMD) patients with stem cells. [DMD INSPIRE] Press Release

Head of Prestigious Ancient DNA Lab Suspended amid Bullying Allegations

The leader of Australia’s premier ancient DNA lab, Alan Cooper, has been suspended following a probe into the ‘culture’ of the center and amid allegations of bullying from his co-workers. Cooper is renowned for reconstructing how humans populated the planet using ancient DNA. [Nature News] Editorial

Hundreds of Extreme Self-Citing Scientists Revealed in New Database

A data set, which lists around 100,000 researchers, shows that at least 250 scientists have amassed more than 50% of their citations from themselves or their co-authors, while the median self-citation rate is 12.7%. The study could help to flag potential extreme self-promoters, and possibly ‘citation farms’, in which clusters of scientists massively cite each other, say the researchers. [Nature News] Editorial

For a Decade, Francis Collins Has Shielded NIH—While Making Waves of His Own

Collins has helped shield the National Institutes of Health (NIH) from threatened budget cuts as well as the upheaval that has shaken many other federal agencies under the Trump administration. [Nature News] Editorial

NEW American Society for Bone and Mineral Research (ASBMR) 2019 Annual Meeting
September 20-23, 2019
Orlando, Florida, United States

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

NEW Postdoctoral Researcher – Ion Channels in Vascular Smooth Muscle (The University of Tennessee)

Scientific Communications Coordinator (STEMCELL Technologies Inc.)

Assistant Professor – Applied Cardiovascular Physiology (York University)

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

Postdoctoral Fellow – Cardiovascular Physiology (University of California, San Diego)

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

Postdoctoral Fellow – Cardiovascular Biology (Oklahoma Medical Research Foundation)

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 Fellow – Facioscapulohumeral Muscular Dystrophy Research (Pfizer)

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.