Network Integration and Modeling of Dynamic Drug Responses at Multi-Omics Levels

Scientists challenged network modeling with time-resolved proteome, transcriptome and methylome measurements in iPSC-derived human 3D cardiac microtissues to elucidate adverse mechanisms of anthracycline cardiotoxicity measured with four different drugs.
[Communications Biology]
Selevsek, N., Caiment, F., Nudischer, R., Gmuender, H., Agarkova, I., Atkinson, F. L., Bachmann, I., Baier, V., Barel, G., Bauer, C., Boerno, S., Bosc, N., Clayton, O., Cordes, H., Deeb, S., Gotta, S., Guye, P., Hersey, A., Hunter, F. M. I., … Kleinjans, J. (2020). Network integration and modelling of dynamic drug responses at multi-omics levels. Communications Biology, 3(1), 1–15. https://doi.org/10.1038/s42003-020-01302-8 Cite
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Dystrophin Dp71ab Is Monoclonally Expressed in Human Satellite Cells and Enhances Proliferation of Myoblast Cells

Dp71ab, but not Dp71, was found to be a molecular enhancer of myoblast proliferation and transfection with Dp71ab may generate a high yield of stem cells for Duchenne muscular dystrophy treatment.
[Scientific Reports]
Farea, M., Rani, A. Q. M., Maeta, K., Nishio, H., & Matsuo, M. (2020). Dystrophin Dp71ab is monoclonally expressed in human satellite cells and enhances proliferation of myoblast cells. Scientific Reports, 10(1), 17123. https://doi.org/10.1038/s41598-020-74157-y Cite
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Inhibition of Aquaporin-1 Prevents Myocardial Remodeling by Blocking the Transmembrane Transport of Hydrogen Peroxide

Researchers showed that hydrogen peroxide (H2O2), produced extracellularly, was necessary for the hypertrophic response of isolated cardiac myocytes and that aquaporin-1 facilitated the transmembrane transport of H2O2 through its water pore, resulting in activation of oxidant-sensitive kinases in cardiac myocytes.
[Science Translational Medicine]
Montiel, V., Bella, R., Michel, L. Y. M., Esfahani, H., Mulder, D. D., Robinson, E. L., Deglasse, J.-P., Tiburcy, M., Chow, P. H., Jonas, J.-C., Gilon, P., Steinhorn, B., Michel, T., Beauloye, C., Bertrand, L., Farah, C., Zotti, F. D., Debaix, H., Bouzin, C., … Balligand, J.-L. (2020). Inhibition of aquaporin-1 prevents myocardial remodeling by blocking the transmembrane transport of hydrogen peroxide. Science Translational Medicine, 12(564). https://doi.org/10.1126/scitranslmed.aay2176 Cite
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Hydrojet-Based Delivery of Footprint-Free iPSC-Derived Cardiomyocytes Into Porcine Myocardium

Scientists analyzed the applicability of a hydrojet-based method to deliver footprint-free iPSC-derived cardiomyocytes into the myocardium.
[Scientific Reports]
Weber, M., Fech, A., Jäger, L., Steinle, H., Bühler, L., Perl, R. M., Martirosian, P., Mehling, R., Sonanini, D., Aicher, W. K., Nikolaou, K., Schlensak, C., Enderle, M. D., Wendel, H. P., Linzenbold, W., & Avci-Adali, M. (2020). Hydrojet-based delivery of footprint-free iPSC-derived cardiomyocytes into porcine myocardium. Scientific Reports, 10(1), 16787. https://doi.org/10.1038/s41598-020-73693-x Cite
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Minimal Contribution of IP3R2 in Cardiac Differentiation and Derived Ventricular-Like Myocytes from Human Embryonic Stem Cells

Scientists investigated the role of Type 2 inositol 1,4,5-trisphosphate receptor (IP3R2) in the differentiation of human embryonic stem cells (hESCs) to cardiomyocytes and in the hESC-derived cardiomyocytes.
[Acta Pharmacologica Sinica]
Zhang, P., Huang, J., Ou-yang, K., Liang, H., Li, M., Wang, Y., & Yang, H. (2020). Minimal contribution of IP 3 R2 in cardiac differentiation and derived ventricular-like myocytes from human embryonic stem cells. Acta Pharmacologica Sinica, 1–11. https://doi.org/10.1038/s41401-020-00528-w Cite
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Targeting Myostatin/Activin A Protects against Skeletal Muscle and Bone Loss during Spaceflight

The authors used both genetic and pharmacological approaches to investigate the effect of targeting myostatin/activin A signaling in mice that were sent to the International Space Station.
[Proceedings of the National Academy of Sciences of the United States of America]
Lee, S.-J., Lehar, A., Meir, J. U., Koch, C., Morgan, A., Warren, L. E., Rydzik, R., Youngstrom, D. W., Chandok, H., George, J., Gogain, J., Michaud, M., Stoklasek, T. A., Liu, Y., & Germain-Lee, E. L. (2020). Targeting myostatin/activin A protects against skeletal muscle and bone loss during spaceflight. Proceedings of the National Academy of Sciences, 117(38), 23942–23951. https://doi.org/10.1073/pnas.2014716117 Cite
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Dioxin Disrupts Dynamic DNA Methylation Patterns in Genes that Govern Cardiomyocyte Maturation

To test the hypothesis that the disruption caused by tetrachlorodibenzo-p-dioxin in the heart results from changes in DNA methylation and gene expression patterns of cardiomyocytes, researchers established a stable mouse embryonic stem cell line expressing a puromycin resistance selectable marker under control of the cardiomyocyte-specific Nkx2-5 promoter.
[Toxicological Sciences]
de Gannes, M., Ko, C.-I., Zhang, X., Biesiada, J., Niu, L., Koch, S. E., Medvedovic, M., Rubinstein, J., & Puga, A. (n.d.). Dioxin Disrupts Dynamic DNA Methylation Patterns in Genes that Govern Cardiomyocyte Maturation. Toxicological Sciences. https://doi.org/10.1093/toxsci/kfaa153 Cite
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Effects of Fibrillin Mutations on the Behavior of Heart Muscle Cells in Marfan Syndrome

Both induced pluripotent stem cells derived from a Marfan syndrome (MFS)-patient and the line with the corrected fibrillin-1 mutation were differentiated to cardiomyocytes. Several functional analyses were performed on this model to study MFS related cardiomyopathy.
[Scientific Reports]
Aalders, J., Léger, L., Van der Meeren, L., Van den Vreken, N., Skirtach, A. G., Sinha, S., De Backer, J., & van Hengel, J. (2020). Effects of fibrillin mutations on the behavior of heart muscle cells in Marfan syndrome. Scientific Reports, 10(1), 16756. https://doi.org/10.1038/s41598-020-73802-w Cite
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The Rho-GEF PIX-1 Directs Assembly or Stability of Lateral Attachment Structures between Muscle Cells

Researchers showed that a PIX protein has an important function in muscle. From a genetic screen in C. elegans, they found that pix-1 was required for the assembly of integrin adhesion complexes at borders between muscle cells, and was required for locomotion of the animal.
[Nature Communications]
Moody, J. C., Qadota, H., Reedy, A. R., Okafor, C. D., Shanmugan, N., Matsunaga, Y., Christian, C. J., Ortlund, E. A., & Benian, G. M. (2020). The Rho-GEF PIX-1 directs assembly or stability of lateral attachment structures between muscle cells. Nature Communications, 11(1), 5010. https://doi.org/10.1038/s41467-020-18852-4 Cite
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MiR-324-5p Inhibits C2C12 Myoblasts Differentiation and Promotes Intramuscular Lipid Deposition through LncDUM and PM20D1, Respectively

Scientists investigated the role of mmu-miR-324-5p in the differentiation of C2C12 myoblasts and lipid droplet deposition in myotubes for future targeted therapies.
[Molecular Therapy-Nucleic Acids]
Liu, Y., Wang, J., Zhou, X., Cao, H., Zhang, X., Huang, K., Li, X., Yang, G., & Shi, X. (2020). MiR-324-5p inhibits C2C12 myoblasts differentiation and promotes intramuscular lipid deposition through LncDUM and PM20D1, respectively. Molecular Therapy - Nucleic Acids, 0(0). https://doi.org/10.1016/j.omtn.2020.09.037 Cite
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Tamoxifen Accelerates Endothelial Healing by Targeting ERα in Smooth Muscle Cell

Using three complementary mouse models of carotid artery injury, researchers demonstrated that both tamoxifen and estradiol accelerated endothelial healing, but only tamoxifen required the presence of the underlying medial smooth muscle cells.
[Circulation Research]
Zahreddine Rana, Davezac Morgane, Smirnova Natalia F, Buscato Mélissa, Lhuillier Emeline, Lupieri Adrien, Solinhac Romain, Vinel Alexia, Vessieres Emilie, Henrion Daniel, Renault Marie-Ange, Gadeau Alain-Pierre, Flouriot Gilles, Lenfant Francoise, Laffargue Muriel, Metivier Raphael, Arnal Jean-Francois, & Fontaine Coralie. (n.d.). Tamoxifen Accelerates Endothelial Healing by Targeting ERα in Smooth Muscle Cell. Circulation Research, 0(0). https://doi.org/10.1161/CIRCRESAHA.120.317062 Cite
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