Muscle Cell News Volume 3.02 | Jan 22 2018

TOP STORY

The MTM1-UBQLN2-HSP Complex Mediates Degradation of Misfolded Intermediate Filaments in Skeletal Muscle

Scientists describe a process by which muscle cells degrade the misfolded intermediate filament proteins desmin and vimentin by the proteasome. This relies on the MTM1-UBQLN2 complex to recognize and guide these misfolded proteins to the proteasome and occurs prior to aggregate formation. [Nat Cell Biol] Abstract

(Ranked by impact factor of the journal)

CARDIAC MUSCLE CELLS

Protein Phosphatase 5 Regulates Titin Phosphorylation and Function at a Sarcomere-Associated Mechanosensor Complex in Cardiomyocytes

The authors showed that protein phosphatase 5 (PP5) binds and dephosphorylates the elastic N2B-unique sequence (N2Bus) of titin in cardiomyocytes. Using various binding and phosphorylation tests, cell-culture manipulation, and transgenic mouse hearts, they demonstrated that PP5 associates with N2Bus in vitro and in sarcomeres and is antagonistic to several protein kinases, which phosphorylate N2Bus and lower titin-based passive tension. [Nat Commun] Full Article

Single-Cell Transcriptional Profiling Reveals Cellular Diversity and Intercommunication in the Mouse Heart

Scientists characterized single-cell transcriptional profiles of the murine non-myocyte cardiac cellular landscape using single-cell RNA sequencing. Detailed molecular analyses revealed the diversity of the cardiac cellulome and facilitated the development of techniques to isolate understudied cardiac cell populations, such as mural cells and glia. [Cell Rep] Full Article | Press Release | Graphical Abstract

EGFR Activation Triggers Cellular Hypertrophy and Lysosomal Disease in NAGLU-Depleted Cardiomyoblasts, Mimicking the Hallmarks of Mucopolysaccharidosis IIIB

To address the molecular mechanisms governing cardiac dysfunctions in mucopolysaccharidosis IIIB, investigators generated a model of the disease by silencing α-N-acetylglucosaminidase (NAGLU) gene expression in H9C2 rat cardiomyoblasts. NAGLU-depleted H9C2 exhibited accumulation of abnormal lysosomes and a hypertrophic phenotype. [Cell Death Dis] Full Article

SKELETAL MUSCLE CELLS

The Effect of Differentiation and TGFβ on Mitochondrial Respiration and Mitochondrial Enzyme Abundance in Cultured Primary Human Skeletal Muscle Cells

Researchers present a streamlined workflow optimized for investigation of primary human skeletal muscle cells. They applied the workflow to differentiated and undifferentiated cells and they investigated the effect of TGFβ1 treatment. [Sci Rep] Full Article

Efficient Differentiation of Human Pluripotent Stem Cells into Skeletal Muscle Cells by Combining RNA-Based MYOD1-Expression and POU5F1-Silencing

Investigators showed a rapid and robust method to induce myogenic differentiation of human pluripotent stem cells by introducing mRNA encoding MYOD1 together with siRNA-mediated knockdown of POU5F1. This integration-free approach generated functional skeletal myotubes with sarcomere-like structure and a fusion capacity in several days. [Sci Rep] Full Article

A Novel Human Muscle Cell Model of Duchenne Muscular Dystrophy Created by CRISPR/Cas9 and Evaluation of Antisense-Mediated Exon Skipping

The authors generated a novel immortalized Duchenne muscular dystrophy (DMD) muscle cell line from the human rhabdomyosarcoma (RD) cell line. They removed DMD exons 51–57 in the RD cell line using the CRISPR/Cas9 system. [J Hum Genet] Abstract

SMOOTH MUSCLE CELLS

LIM and Cysteine-Rich Domains 1 Is Required for Thrombin-Induced Smooth Muscle Cell Proliferation and Promotes Atherogenesis

In exploring the molecular mechanisms underlying restenosis, scientists identified LIM and cysteine-rich domains 1 (LMCD1) as a gene highly responsive to thrombin in human aortic smooth muscle cells. LMCD1 depletion inhibited proliferation of human but not murine vascular smooth muscle cells. [J Biol Chem] Abstract | Full Article

Inhibition of miR-361-5p Suppressed Pulmonary Artery Smooth Muscle Cell Survival and Migration by Targeting ABCA1 and Inhibiting the JAK2/STAT3 Pathway

Researchers investigated the effect of miR-361-5p on the proliferation, migration and apoptosis of pulmonary artery smooth muscle cells (PASMCs) that under the treatment of hypoxia and explored the underlying mechanisms. The results proved that hypoxia noticeably up-regulated the expression of miR-361-5p in PASMCs in comparison to the normoxia-treated cells, while TNF-α and IL-6 stimulation had no obvious effects on miR-361-5p level. [Exp Cell Res] Abstract

Gliclazide, a K_ATP Channel Blocker, Inhibits Vascular Smooth Muscle Cell Proliferation through the CaMKKβ-AMPK Pathway

Scientists investigated the inhibitory effect of gliclazide on vascular smooth muscle cell (VSMC) proliferation and tried to identify the underlying signaling pathway. K_ATP channel openers and Kir6.1 siRNA prevented gliclazide-mediated inhibition of VSMC proliferation. [Vascul Pharmacol] Abstract | Graphical Abstract

Mustn1: A Developmentally Regulated Pan-Musculoskeletal Cell Marker and Regulatory Gene

The author summarizes current knowledge of Mustn1 and proposes that it is a new developmentally regulated pan-musculoskeletal marker, as well as a key regulatory protein for cell differentiation and tissue growth. [Int J Mol Sci] Full Article

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

First Duchenne Muscular Dystrophy Patient Dosed in Systemic Microdystrophin Gene Therapy

Parent Project Muscular Dystrophy (PPMD) announced that the first Duchenne patient has been dosed with microdystrophin gene therapy by Dr. Jerry Mendell, Dr. Louise Rodino-Klapac, and their team at Nationwide Children’s Hospital. This trial was funded in part by a $2.2 million grant from PPMD in early 2017 as part of the organization’s Gene Therapy Initiative. [Parent Project Muscular Dystrophy (PR Newswire Association LLC.)] Press Release

Benitec Receives U.S. Orphan Drug Designation for BB-301, Its ddRNAi Therapeutic for the Treatment of Oculopharyngeal Muscular Dystrophy

Benitec Biopharma Limited announced that the FDA has granted Orphan Drug Designation to BB-301 for the treatment of oculopharyngeal muscular dystrophy. [Benitec Biopharma Limited] Press Release

U.S. Scientists Breathe a Sigh of Relief as Government Shutdown to End

It’s over—at least for the moment. The U.S. Senate voted 81–18 to advance legislation funding government activities, essentially ending a partial government shutdown that had moved into its third day. The House of Representatives is expected to follow suit, sending the bill to President Donald Trump for his signature. [ScienceInsider] Editorial

Online Tool Calculates Reproducibility Scores of PubMed Papers

A new online tool measures the reproducibility of published scientific papers by analyzing data about articles that cite them. The software comes at a time when scientific societies and journals are alarmed by evidence that findings in many published articles are not reproducible and are struggling to find reliable methods to evaluate whether they are. [ScienceInsider] Editorial

India’s Education Minister Assails Evolutionary Theory, Calls for Curricula Overhaul

A new front has opened in the war on science in India. India’s minister for higher education, Satyapal Singh, took aim at the theory of evolution. Calling himself “a responsible man of science,” Singh, a chemist, suggested that Darwin’s theory is “scientifically wrong” and “needs to change” in school and university curricula. [ScienceInsider] Editorial

NEW Weinstein 2018: Cardiovascular Development and Regeneration Conference
May 16-18, 2018
Nara, Japan

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

NEW Postdoctoral Fellow – Metabolic Regulation (Harvard University)

Research Fellow – Rhabdomyosarcoma (Massachusetts General Hospital)

Research Assistant – Cardiovascular Stem Cells (University of Oxford)

Postdoctoral Position – Cardiac Fibrosis (Centre National de la Recherche Scientifique)

Research Assistant – Muscular Dystrophy (University of Oxford)

Faculty Position – Translational Research in Cardiac Biology (Temple University)

Postdoctoral Fellowship – Mass Spectrometry of Cardiomyocytes (Medical College of Wisconsin)

Postdoctoral Research Associate – Molecular and Integrative Cardiology and Muscle Biology (University of Minnesota Medical School)

Postdoctoral Positions – Cardiac Tissue Homeostasis and Regeneration Mechanisms (Centro Nacional de Investigaciones Cardiovasculares)

Postdoctoral Associate – Cardiovascular Regenerative Medicine (Duke University)

Postdoctoral Position – Cardiovascular Biology (Icahn School of Medicine at Mount Sinai)

Postdoctoral Position – Cardiac Metabolism (University of British Columbia)

Postdoctoral Position – Biomicrofluidics and Organ-on-a-Chip Research (University of Toronto)

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.