Muscle Cell News Volume 4.27 | Aug 12 2019

TOP STORY

Atheroprotective Roles of Smooth Muscle Cell Phenotypic Modulation and the TCF21 Disease Gene as Revealed by Single-Cell Analysis

Using single-cell RNA sequencing, researchers comprehensively characterized the transcriptomic phenotype of modulated smooth muscle cells in vivo in atherosclerotic lesions of both mouse and human arteries and found that these cells transformed into unique fibroblast-like cells, termed ‘fibromyocytes’, rather than into a classical macrophage phenotype. [Nat Med] Abstract

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CARDIAC MUSCLE CELLS

Epicardial Cells Derived from Human Embryonic Stem Cells Augment Cardiomyocyte-Driven Heart Regeneration

Investigators tested the ability of human embryonic stem cell (hESC)-derived epicardium to augment the structure and function of engineered heart tissue in vitro and to improve efficacy of hESC-cardiomyocyte grafts in infarcted athymic rat hearts. Epicardial cells markedly enhanced the contractility, myofibril structure and calcium handling of human engineered heart tissues, while reducing passive stiffness compared with mesenchymal stromal cells. [Nat Biotechnol] Abstract | Press Release

Chromatin Compartment Dynamics in a Haploinsufficient Model of Cardiac Laminopathy

The authors performed genome-wide chromosome conformation analyses in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) with a haploinsufficient mutation for lamin A/C. Compared with gene-corrected cells, mutant hiPSC-CMs had marked electrophysiological and contractile alterations, with modest gene expression changes. [J Cell Biol] Abstract

Select Septate Junction Proteins Direct ROS-Mediated Paracrine Regulation of Drosophila Cardiac Function

Scientists found that in pericardial cells (PCs), Coracle (Cora) and Kune-kune (Kune) were altered in abundance in response to manipulations of reactive oxygen species (ROS)-p38 signaling. Genetic analyses established Cora and Kune as key effectors of ROS-p38 signaling in PCs on proper heart function. [Cell Rep] Full Article | Graphical Abstract

Landscape of Enhancer-Enhancer Cooperative Regulation during Human Cardiac Commitment

Researchers filtered robust enhancers in ESC through integrating bidirectional transcription, genomic location and epigenetic modification. Genome-wide enhancer-enhancer interactions were then identified based on enhancer-promoter relationships that were derived from Hi-C data. [Mol Ther Nucleic Acids] Abstract | Full Article

Reprogramming of Urine-Derived Renal Epithelial Cells into iPSCs Using Self-Replicating RNA and Consecutive Differentiation into Beating Cardiomyocytes

Footprint-free induced pluripotent stem cells were successfully generated from urine-derived renal epithelial cells through a single application of self-replicating RNA. The expression of pluripotency markers and the in vitro as well as in vivo trilineage differentiation was demonstrated. [Mol Ther Nucleic Acids] Abstract

A Human Stem Cell Model of Fabry Disease Implicates LIMP-2 Accumulation in Cardiomyocyte Pathology

An in vitro model recapitulated clinical data with Fabry disease (FD) cardiomyocytes accumulating GL-3 and displaying an increased excitability, with altered electrophysiology and calcium handling. Quantitative proteomics enabled the identification of >5,500 proteins in the cardiomyocyte proteome and secretome, and revealed accumulation of the lysosomal protein LIMP-2 and secretion of cathepsin F and HSPA2/HSP70-2 in FD. [Stem Cell Reports] Full Article | Graphical Abstract

Comparing Human iPSC-Cardiomyocytes versus HEK293T Cells Unveils Disease-Causing Effects of Brugada Mutation A735V of Na_V1.5 Sodium Channels

Investigators engineered human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) carrying the CRISPR/Cas9 introduced BrS-mutation p.A735V-Na_V1.5 as a novel model independent of a patient´s genetic background. Long-term cultivation of hiPSC-CMs on a stiff matrix was applied to promote maturation. [Sci Rep] Full Article

SKELETAL MUSCLE CELLS

ULK2 Is Essential for Degradation of Ubiquitinated Protein Aggregates and Homeostasis in Skeletal Muscle

Using an unbiased expression analysis of 34 putative autophagy genes across mouse tissues, the authors identified unc-51 like autophagy activating kinase (Ulk)2, a homolog of the yeast autophagy related protein 1, as particularly enriched in skeletal muscle. Subsequent experiments revealed accumulations of insoluble ubiquitinated protein aggregates associated with the adaptors sequestosome 1 and next to breast cancer type 1 susceptibility protein gene 1 protein in adult muscles with ULK2 deficiency. [FASEB J] Abstract

SMOOTH MUSCLE CELLS

Single-Cell RNA-Seq of the Developing Cardiac Outflow Tract Reveals Convergent Development of the Vascular Smooth Muscle Cells

Investigators performed single-cell transcriptomic sequencing of 55,611 mouse cardiac outflow tract (OFT) cells from three developmental stages that generally corresponded to the early, middle, and late stages of OFT remodeling and septation. Known cellular transitions, such as endothelial-to-mesenchymal transition, were recapitulated. [Cell Rep] Full Article | Graphical Abstract

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Reassessing the Role of Diacylglycerols in Insulin Resistance

Skeletal muscle (SM) insulin resistance (IR) plays an important role in the burden of obesity, particularly because it leads to glucose intolerance and type 2 diabetes. Given that SM accounts for the majority of insulin-stimulated glucose uptake, the authors integrate recent observational and mechanistic works with the sole focus on questioning the role of diacylglycerols in SM IR. [Trends Endocrinol Metab] Abstract

Integrin Signaling: Linking Mechanical Stimulation to Skeletal Muscle Hypertrophy

Scientists provide basic information about integrin structure and activation, then explores its potential to serve as a critical mechanosensor and activator of muscle protein synthesis and growth. Overall, the hypothesis is proposed that the α7β1 integrin can contribute to mechanical-load induced skeletal muscle growth via an mTORC1-independent mechanism. [Am J Physiol Cell Physiol] Abstract

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

Capricor Therapeutics Announces Positive DSMB Safety and Futility Review and Continuation of Its HOPE-2 Study in Duchenne Muscular Dystrophy

Capricor Therapeutics, Inc. announced that its independent DSMB completed its safety assessment and futility analysis review of the company’s ongoing Phase II HOPE-2 study with CAP-1002 in boys and young men who are in advanced stages of Duchenne muscular dystrophy and recommended that the trial continue. [Capricor Therapeutics, Inc.] Press Release

Numerate Receives $2 Million SBIR Phase II Award to Continue Research Using Its AI-Driven Discovery Platform to Identify New Antiarrhythmic Drug

The National Heart, Lung, and Blood Institute of the National Institutes of Healt has awarded a $2 million Small Business Innovation Research Phase II grant to Numerate, following successful completion of their work funded by a Phase I Award. Collaborating with members of the UCLA Cardiovascular Research Laboratory, Numerate will use the funds to support the discovery of novel, small molecule drug candidates that address the need for a well-tolerated anti-arrhythmic therapy for the treatment and prevention of ventricular tachycardias and fibrillation. [Numerate] Press Release

Senators Blast Novartis over Data Manipulation before Approval of Zolgensma

A group of senators, including presidential hopefuls Sens. Elizabeth Warren and Bernie Sanders, blasted Novartis for failing to promptly disclose that falsified data were used to win approval for the company’s $2.1 million gene therapy, Zolgensma. [STAT News] Editorial

Academia to FBI on Monitoring Chinese Scientists: “Tread Carefully”

Nearly two dozen higher education groups warn the government to be cautious when advising US research universities to keep an eye on students and faculty with ties to certain Chinese institutions. [The Scientist] Editorial

UK Announces Fast-Track Visa to Recruit Top Scientists

British Prime Minister Boris Johnson has announced a new fast-track visa to attract elite scientists to live and work in the UK, in light of the nation leaving the European Union later this year. “I want the UK to continue to be a global science superpower, and when we leave the EU we will support science and research and ensure that, far from losing out, the scientific community has a huge opportunity to develop and export our innovation around the world,” Johnson said in a statement. [The Scientist] Editorial

NEW Hypoxia: Molecules, Mechanisms and Disease
January 19-23, 2020
Keystone, Colorado, United States

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NEW Assistant Professor – Applied Cardiovascular Physiology (York University)

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

Scientific Communications Coordinator (STEMCELL Technologies Inc.)

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 Researchers – Cardiovascular Studies (Virginia Tech)

Postdoctoral Fellow – Facioscapulohumeral Muscular Dystrophy Research (Pfizer)

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