MicroRNAs promote skeletal muscle differentiation of mesodermal iPSC-derived progenitors

Giorgia Giacomazzi, Bryan Holvoet, Sander Trenson, Ellen Caluwé, Bojana Kravic, Hanne Grosemans, Álvaro Cortés-Calabuig, Christophe M. Deroose, Danny Huylebroeck, Said Hashemolhosseini, Stefan Janssens, Elizabeth McNally, Mattia Quattrocelli and Maurilio Sampaolesi ()
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Giorgia Giacomazzi: Department of Development and Regeneration, KU Leuven
Bryan Holvoet: Nuclear Medicine and Molecular Imaging, KU Leuven
Sander Trenson: Department of Cardiovascular Sciences, KU Leuven
Ellen Caluwé: Department of Cardiovascular Sciences, KU Leuven
Bojana Kravic: Friedrich-Alexander University of Erlangen-Nürnberg
Hanne Grosemans: Department of Development and Regeneration, KU Leuven
Álvaro Cortés-Calabuig: Center for Human Genetics KU Leuven
Christophe M. Deroose: Nuclear Medicine and Molecular Imaging, KU Leuven
Danny Huylebroeck: Erasmus MC
Said Hashemolhosseini: Friedrich-Alexander University of Erlangen-Nürnberg
Stefan Janssens: Department of Cardiovascular Sciences, KU Leuven
Elizabeth McNally: Northwestern University
Mattia Quattrocelli: Department of Development and Regeneration, KU Leuven
Maurilio Sampaolesi: Department of Development and Regeneration, KU Leuven

Nature Communications, 2017, vol. 8, issue 1, 1-14

Abstract: Abstract Muscular dystrophies (MDs) are often characterized by impairment of both skeletal and cardiac muscle. Regenerative strategies for both compartments therefore constitute a therapeutic avenue. Mesodermal iPSC-derived progenitors (MiPs) can regenerate both striated muscle types simultaneously in mice. Importantly, MiP myogenic propensity is influenced by somatic lineage retention. However, it is still unknown whether human MiPs have in vivo potential. Furthermore, methods to enhance the intrinsic myogenic properties of MiPs are likely needed, given the scope and need to correct large amounts of muscle in the MDs. Here, we document that human MiPs can successfully engraft into the skeletal muscle and hearts of dystrophic mice. Utilizing non-invasive live imaging and selectively induced apoptosis, we report evidence of striated muscle regeneration in vivo in mice by human MiPs. Finally, combining RNA-seq and miRNA-seq data, we define miRNA cocktails that promote the myogenic potential of human MiPs.

Date: 2017
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DOI: 10.1038/s41467-017-01359-w

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