Muscle Cell News Volume 4.14 | Apr 22 2019

TOP STORY

PAX3 Confers Functional Heterogeneity in Skeletal Muscle Stem Cell Responses to Environmental Stress

Investigators evaluated the impact of 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure, a ubiquitous and highly toxic pollutant, on muscle satellite cells (MuSCs) by combining in vivo mouse molecular genetic models with ex vivo studies. While all MuSCs expressed the transcription factor PAX7, investigators showed that a subset also expressed PAX3 and exhibited resistance to environmental stress. [Cell Stem Cell] Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

CARDIAC MUSCLE CELLS

Therapeutic Role of miR-19a/19b in Cardiac Regeneration and Protection from Myocardial Infarction

Researchers reported that expression of miR-19a/19b, members of the miR-17-92 cluster, was induced in heart failure patients. They showed that intra-cardiac injection of miR-19a/19b enhanced cardiomyocyte proliferation and stimulated cardiac regeneration in response to myocardial infarction injury. [Nat Commun] Full Article

Cardiomyocyte Glucocorticoid and Mineralocorticoid Receptors Directly and Antagonistically Regulate Heart Disease in Mice

To examine the specific and coordinated roles that glucocorticoid receptors (GR) and mineralocorticoid receptors (MR) play in mediating the direct effects of stress on the heart, scientists generated mice with cardiomyocyte-specific deletion of GR (cardioGRKO), MR, or both GR and MR. The cardioGRKO mice spontaneously developed cardiac hypertrophy and left ventricular systolic dysfunction and died prematurely from heart failure. [Sci Signal] Full Article

Heparanase Protects the Heart against Chemical or Ischemia/Reperfusion Injury

Transcriptomic analysis of Hep-tg hearts revealed that 240 genes related to the stress response, immune response, cell death, and development were altered in a pro-survival direction encompassing genes promoting the unfolded protein response and autophagy, as well as those protecting against oxidative stress. [J Mol Cell Cardiol] Abstract

Yin-Yang 1 Transcription Factor Modulates ST2 Expression during Adverse Cardiac Remodeling Post-Myocardial Infarction

Myocardial infarction (MI) was induced in Wistar rats randomly receiving metformin or saline solution by permanent ligation of the left anterior coronary artery. In addition, a model of cardiomyocyte “biochemical strain” was used. Metformin administration improved post-MI cardiac remodeling, an effect that was associated with increased interleukin-33 and reduced sST2 levels in the myocardium. [J Mol Cell Cardiol] Abstract

SKELETAL MUSCLE CELLS

Lineage Tracing Reveals a Subset of Reserve Muscle Stem Cells Capable of Clonal Expansion under Stress

Researchers identified a minor subset of Pax7⁺ skeletal muscle satellite cells (SCs) that was indelibly marked by an inducible Mx1-Cre transgene in vivo, was enriched for Pax3 expression, and had reduced reactive oxygen species levels. Mx1⁺ SCs possessed potent stem cell activity upon transplantation but minimally contributed to endogenous muscle repair, due to their relative low abundance. [Cell Stem Cell] Abstract | Graphical Abstract

Time of Exercise Specifies the Impact on Muscle Metabolic Pathways and Systemic Energy Homeostasis

Using high-throughput transcriptomic and metabolomic approaches, scientists identified distinct responses of metabolic oscillations that characterized exercise in either the early rest phase or the early active phase in mice. Notably, glycolytic activation was specific to exercise at the active phase. [Cell Metab] Abstract | Graphical Abstract

Physiological and Molecular Dissection of Daily Variance in Exercise Capacity

The authors found that both mice and humans exhibited daytime variance in exercise capacity between the early and late part of their active phase. The daytime variance in mice was dependent on exercise intensity and relied on the circadian clock proteins PER1/2. High-throughput gene expression and metabolic profiling of skeletal muscle revealed metabolic pathways that are differently activated upon exercise in a daytime-dependent manner. [Cell Metab] Full Article | Graphical Abstract

Single Cell Analysis of Adult Mouse Skeletal Muscle Stem Cells in Homeostatic and Regenerative Conditions

Researchers were able to compare the transcriptomes of thousands of muscle stem cells (MuSCs) and primary myoblasts isolated from homeostatic or regenerating muscles by single cell RNA sequencing. Using computational approaches, they could reconstruct dynamic trajectories and place, in a pseudotemporal manner, the transcriptomes of individual MuSC within these trajectories. [Development] Abstract

Myristic Acid Specifically Stabilizes Diacylglycerol Kinase δ Protein in C2C12 Skeletal Muscle Cells

Investigators characterized the myristic acid-dependent increase of diacylglycerol kinase δ (DGKδ) protein. A cycloheximide chase assay demonstrated that myristic acid, but not palmitic acid, markedly stabilized DGKδ protein. Moreover, other DGK isozymes, DGKη and ζ, as well as glucose uptake-related proteins, such as protein kinase C α, protein kinase C ζ, Akt and glycogen synthase kinase 3β, failed to be stabilized by myristic acid. [Biochim Biophys Acta] Abstract | Graphical Abstract

Clusterin Silencing Restores Myoblasts Viability and down Modulates the Inflammatory Process in Osteoporotic Disease

Vastus lateralis muscle biopsies were collected from 20 women with osteoporosis (OP) undergoing surgery for fragility hip fracture and 20 women undergoing arthroplasty for hip osteoarthritis. Scientists found an overexpression of clusterin in degenerated fibers in OP closely correlated with interleukin 6 and histone H4 acetylation level. [J Transl Med] Full Article

Dermatopontin in Skeletal Muscle Extracellular Matrix Regulates Myogenesis

Investigators explored the role of dermatopontin (DPT) in myogenesis and perceived that it enhanced cell adhesion, reduced cell proliferation and promoted myoblast differentiation in C2C12 cells. Their results revealed an inhibitory effect with fibronectin in myoblast differentiation. They also observed that DPT and fibromodulin regulated positively to each other and promoted myogenic differentiation. [Cells] Full Article

SMOOTH MUSCLE CELLS

The Stat3-Fam3a Axis Promotes Muscle Stem Cell Myogenic Lineage Progression by Inducing Mitochondrial Respiration

Researchers demonstrated that Stat3 promoted muscle stem cell myogenic lineage progression by stimulating mitochondrial respiration in mice. They identified Fam3a, a cytokine-like protein, as a major Stat3 downstream effector in muscle stem cells. They demonstrated that Fam3a was required for muscle stem cell commitment and skeletal muscle development. [Nat Commun] Full Article | Press Release

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

Healthy Skeletal Muscle Aging: The Role of Satellite Cells, Somatic Mutations and Exercise

The authors focus on human studies, but include cellular and animal models, to describe the role of satellite cells (SC) in different physiological scenarios relevant for human aging. The intrinsic and extrinsic mechanisms underlying age-induced alterations in the SC pool are discussed, with particular emphasis on the genomic modifications that accumulate in human SCs during a lifetime (i.e., somatic mutation-burden). [Int Rev Cell Mol Biol] Abstract

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

Quantum Genomics Receives First Regulatory and Ethics Approvals to Initiate Phase IIb QUORUM Study of Firibastat in Heart Failure

Quantum Genomics announced the first regulatory and ethics approvals for its Phase IIb QUORUM study of firibastat in heart failure. The French National Agency for Medicines and Health Products Safety in France was the first Health Authority to approve the study which will be conducted in seven European countries and in the US. [Quantum Genomics] Press Release

Prothena Reports Results from the Phase III VITAL Amyloidosis Study of NEOD001 (Birtamimab) in AL Amyloidosis

Prothena Corporation plc reported final results from the Phase III VITAL amyloidosis study of NEOD001 in newly diagnosed, treatment naïve patients with AL amyloidosis and cardiac dysfunction, which was discontinued in 2018. [Prothena Corporation plc] Press Release

FibroGen Receives Orphan Drug Designation from the US FDA for Pamrevlumab for the Treatment of Duchenne Muscular Dystrophy

FibroGen, Inc. announced that the FDA has granted Orphan Drug Designation for the company’s anti-CTGF antibody, pamrevlumab, for the treatment of patients with Duchenne muscular dystrophy. Duchenne muscular dystrophy is a rare and debilitating neuromuscular disease that affects between approximately 1 in every 3,500 to 5,000 newborn boys. [FibroGen, Inc.] Press Release

ACEA Biosciences – a Part of Agilent Launches the xCELLigence RTCA ePacer to Improve the Quality and Functionality of hiPSC-Cardiomyocytes for Drug Discovery, Safety Pharmacology, and Cardiac Disease Research

ACEA Biosciences unveiled the new xCELLigence^® RTCA ePacerTM during their workshop held at the Society of Toxicology (SOT) Annual Meeting in Baltimore. [ACEA BIO] Press Release

Framingham Heart Study Awarded $38 Million for the Next 6 Years

The Framingham Heart Study, the nation’s longest running cohort study with longitudinal analysis of cardiovascular disease, has been renewed for an additional six years and $38 million dollars from the National Heart, Lung, and Blood Institute. [Boston University] Press Release

PPMD Awards $100,000 Grant to Nationwide Children’s Hospital to Further Explore GALGT2 Gene Therapy

Drs. Paul Martin and Kevin Flanigan have completed work under a $100,000 grant exploring GALGT2 gene therapy technology as a potential treatment for Duchenne. [Parent Project Muscular Dystrophy] Press Release

How US-China Political Tensions Are Affecting Science

In the latest twist, several US universities are expected this month to announce the actions they have taken against foreign scientists caught breaking rules concerning National Institutes of Health funding, according to comments made by agency director Francis Collins to the Senate Appropriations Committee. [Nature News] Editorial

Stanford Clears Three Faculty Members of ‘CRISPR Babies’ Involvement

Stanford University cleared three faculty members of any misconduct in their interactions with the Chinese scientist who created “CRISPR babies” last year. [STAT News] Editorial

NEW The Smooth Muscle Conference
July 14-19, 2019
West Palm Beach, Florida, United States

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

NEW Postdoctoral Researcher – Proliferative Responses in Cardiac Disease (University of Cambridge)

Senior Research Investigator – Multiple Sclerosis Research (Thomas Jefferson University)

Postdoctoral Positions – Signaling Mechanisms of Muscle Metabolism and Regeneration (McGovern Medical School at University of Texas Health Science Center)

Postdoctoral Scholar – Cardiovascular Genomics (Stanford Medicine)

Early Stage Researchers – Various (Institutions across Europe in the TRIM-NET – ITN Network)

Postdoctoral Research Associate – Cardiovascular Research (Old Dominion University)

Postdoctoral Position – Mechanotransduction in Heart Development and Regeneration (Brown University)

Assistant Professor – Sarcoma or Skeletal Related Malignancies (University of California, Davis)

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

Assistant/Associate Adjunct Professor – Cardiovascular Medicine (University of California, Davis)

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.