Muscle Cell News Volume 4.41 | Dec 9 2019

TOP STORY

Hic1 Defines Quiescent Mesenchymal Progenitor Subpopulations with Distinct Functions and Fates in Skeletal Muscle Regeneration

Researchers identified Hypermethylated in cancer 1 (Hic1) as a marker of mesenchymal progenitors (MPs) in skeletal muscle and further show that Hic1 deletion led to MP hyperplasia. Single-cell RNA-seq and ATAC-seq analysis of Hic1⁺ MPs in skeletal muscle shows multiple subpopulations, which they further showed have distinct functions and lineage potential. [Cell Stem Cell] Full Article | Graphical Abstract

(Ranked by impact factor of the journal)

CARDIAC MUSCLE CELLS

Adult Human Cardiac Stem Cell Supplementation Effectively Increases Contractile Function and Maturation in Human Engineered Cardiac Tissues

Human induced pluripotent stem cell-derived cardiomyocytes (hCMs) were mixed with Collagen/Matrigel to fabricate control human engineered cardiac tissues, with an experimental group of human cardiac stem cells (hCSCs)-supplemented human engineered cardiac tissues fabricated using a 9:1 ratio of hCM to hCSC. Functional testing was performed starting on culture day six, under spontaneous conditions and also during electrical pacing from 0.25 to 1.0Hz, measurements repeated at days eight and ten. [Stem Cell Res Ther] Full Article

Phosphomimetic Cardiac Myosin-Binding Protein C Partially Rescues a Cardiomyopathy Phenotype in Murine Engineered Heart Tissue

Scientists compared the effect of phosphomimetic and wild-type cardiac myosin-binding protein C (cMyBBP-C)gene transfer on the hypertrophic cardiomyopathy phenotype of engineered heart tissues (EHTs) generated from a mouse model carrying a Mybpc3 mutation (KI). KI EHTs showed lower levels of mutant Mybpc3 mRNA and protein, and altered gene expression compared with wild-type EHTs. [Sci Rep] Full Article

Exogenous NADPH Ameliorates Myocardial Ischemia-Reperfusion Injury in Rats Through Activating AMPK/mTOR Pathway

Exogenous NADPH significantly decreased the apoptotic rate of cardiomyocytes, and reduced the cleavage of PARP and caspase-3. In addition, exogenous NADPH reduced mitochondrial vacuolation and increased mitochondrial membrane protein COXIV and TOM20, decreased BNIP3L and increased Bcl-2 to protect mitochondrial function. [Acta Pharmacol Sin] Abstract

SKELETAL MUSCLE CELLS

CRISPR-Cas3 Induces Broad and Unidirectional Genome Editing in Human Cells

Investigators demonstrated that type I-E CRISPR mediated distinct DNA cleavage activity in human cells. Notably, Cas3, which possesses helicase and nuclease activity, predominantly triggered several thousand base pair deletions upstream of the 5′-ARG protospacer adjacent motif, without prominent off-target activity. This Cas3-mediated directional and broad DNA degradation could be used to introduce functional gene knockouts and knock-ins. [Nat Commun] Full Article

Re-Enforcing Hypoxia-Induced Polyploid Cardiomyocytes Enter Cytokinesis Through Activation of β-Catenin

Researchers showed that β-catenin, a key regulator in heart development, could increase cytokinesis in polyploid multinucleated cardiomyocytes (CMs). The activation of β-catenin increased the expression of the cytokinesis-related factor epithelial cell transforming 2, which regulated the actomyosin ring and thus led to the completion of cytokinesis in polyploid CMs. [Sci Rep] Full Article

Adult Human Cardiac Stem Cell Supplementation Effectively Increases Contractile Function and Maturation in Human Engineered Cardiac Tissues

To characterize the function of growth factor receptor-bound 10 (Grb10) and its regulation by mTORC1 in human muscle, primary skeletal muscle cells were isolated from healthy lean young men and then induced to differentiate into myotubes. Knockdown of Grb10 enhanced insulin-induced PI3K/Akt signaling and glucose uptake in myotubes, reinforcing the notion underlying its function as a negative regulator of insulin action in human muscle. [Am J Physiol Endocrinol Metab] Abstract

mTORC2 Affects the Maintenance of the Muscle Stem Cell Pool

Using histological, biochemical, and molecular biological methods, investigators characterized the muscle phenotype of mice depleted for rictor in the Myf5-lineage and of mice depleted for rictor in skeletal muscle fibers. The proliferative and myogenic potential of muscle stem cells was analyzed upon cardiotoxin-induced injury in vivo and in isolated myofibers in vitro. [Skelet Muscle] Full Article

mTORC1 Mediates Lysine-Induced Satellite Cell Activation to Promote Skeletal Muscle Growth

The authors investigated whether satellite cells participate directly in lysine (Lys)-induced skeletal muscle growth and whether the mammalian target of rapamycin complex 1 (mTORC1) pathway was activated both in vivo and in vitro to mediate satellite cell functions in response to Lys supplementation. Subsequently, the skeletal muscle growth of piglets was controlled by dietary Lys supplementation. [Cells] Full Article

SMOOTH MUSCLE CELLS

Adenosine, via A_2B Receptors, Inhibits Human (P-SMC) Progenitor Smooth Muscle Cell Growth

Human progenitor smooth muscle cells (SMCs), 2-chloroadenosine and BAY60-6583 inhibited SMc proliferation and migration. Likewise, increasing endogenous adenosine by blocking adenosine metabolism with erythro-9-(2-hydroxy-3-nonyl) adenine and 5-iodotubercidin attenuated P-SMC proliferation and migration. [Hypertension] Abstract

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S100 Proteins in Atherosclerosis

Some members of the S100 proteins family bind with their receptors, such as advanced glycation end products, scavenger receptors and toll-like receptor 4, contributing to the cellular response in atherosclerotic progression. The authors summarize the roles of S100 proteins in the vascular inflammation, vascular calcification and vascular oxidative stress. [Clin Chim Acta] Abstract

Extracellular Signal-Regulated Kinases 1 and 2 Regulate Neuromuscular Junction and Myofiber Phenotypes in Mammalian Skeletal Muscle

Reciprocal interactions between these excitable cells, and between them and others cell types present within the muscle tissue, shape the development, homeostasis and plasticity of skeletal muscle. An important aim in the field is to understand the molecular mechanisms underlying these cellular interactions, which include identifying the nature of the signals and receptors involved but also of the downstream intracellular signaling cascades elicited by them. [Neurosci Lett] Abstract

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

Axsome Therapeutics Announces AXS-12 Achieves Primary Endpoint in CONCERT Phase II Trial in Narcolepsy

Axsome Therapeutics, Inc. announced that AXS-12 met the prespecified primary endpoint and significantly reduced the number of cataplexy attacks as compared to placebo in patients with narcolepsy in the CONCERT Phase II trial. AXS-12 also significantly reduced excessive daytime sleepiness, and improved cognitive function, sleep quality and sleep-related symptoms. [Axsome Therapeutics, Inc] Press Release

ARCS Foundation Awards $225,000 in Fellowships to UC San Diego Graduate Students

The Achievement Rewards for College Scientists (ARCS) Foundation recently awarded a total of $225,000 to 30 graduate students at the University of California San Diego for the 2019-20 academic year. The annual fellowship awards recognize exceptional students in the natural sciences, engineering and medicine. [San Diego Community News Group] Press Release

Tufts to Remove Sackler Name from Medical Campus

Tufts University will not return donations from the family that made its riches on opioids, but the university will start a $3 million endowment for addiction prevention and treatment. [The Scientist] Editorial

Merck and Sanofi Buy Smaller Cancer Drug Firms at Big Premiums, Fueling Investor Excitement

The drug giants Merck and Sanofi each said they would acquire a smaller drug maker for more than $2 billion – in each case, more than double the smaller company’s market capitalization – cheering investors about large companies’ appetite to execute buyouts in the biotechnology sector. [STAT News] Editorial

House Republicans Fuel Capitol Hill Chaos with Competing Drug Pricing Bill

Republicans are set to accelerate Capitol Hill’s drug pricing chaos with a new proposal to lower the cost of prescription medicines, according to a summary document obtained by STAT. [STAT News] Editorial

NEW Beyond a Million Genomes: From Discovery to Precision Health
January 21-25, 2020
Breckenridge, Colorado, United States

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NEW Postdoctoral Researcher – Muscle Stem Cell Biology (University at Albany)

Postdoctoral Researcher – Skeletal Muscle Aging (St. Jude Children’s Research Hospital)

Senior Scientist – Muscle Cell Biology (Shape Therapeutics)

Asistant Professor – Ion Channels (University of Tennessee)

Assistant Professor – Muscle Biology (Purdue University)

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)

Research Scientist – Metabolic & Muscle Diseases (Regeneron)

Research Scientist – Gene Therapy for Neuromuscular Disorders (Vertex Pharmaceuticals)

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

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