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Mature Myotubes Generated From Human-Induced Pluripotent Stem Cells Without Forced Gene Expression

Fujiwara, Kei Yamamoto, Risa Kubota, Tomoya Tazumi, Atsutoshi Sabuta, Tomoka Takahashi, Masanori P. Sakurai, Hidetoshi 京都大学 DOI:10.3389/fcell.2022.886879

2022

概要

Human-induced pluripotent stem cells (hiPSCs) are a promising tool for disease modeling and drug screening. To apply them to skeletal muscle disorders, it is necessary to establish mature myotubes because the onset of many skeletal muscle disorders is after birth. However, to make mature myotubes, the forced expression of specific genes should be avoided, as otherwise dysregulation of the intracellular networks may occur. Here, we achieved this goal by purifying hiPSC-derived muscle stem cells (iMuSC) by Pax7-fluorescence monitoring and antibody sorting. The resulting myotubes displayed spontaneous self-contraction, aligned sarcomeres, and a triad structure. Notably, the phenotype of sodium channels was changed to the mature type in the course of the differentiation, and a characteristic current pattern was observed. Moreover, the protocol resulted in highly efficient differentiation and high homogeneity and is applicable to drug screening.

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Conflict of Interest: The author AT was employed by Asahi Kasei Pharma

Corporation.

The remaining authors declare that the research was conducted in the absence of

any commercial or financial relationships that could be construed as a potential

conflict of interest.

Publisher’s Note: All claims expressed in this article are solely those of the authors

and do not necessarily represent those of their affiliated organizations, or those of

the publisher, the editors, and the reviewers. Any product that may be evaluated in

this article, or claim that may be made by its manufacturer, is not guaranteed or

endorsed by the publisher.

Copyright © 2022 Fujiwara, Yamamoto, Kubota, Tazumi, Sabuta, Takahashi and

Sakurai. This is an open-access article distributed under the terms of the Creative

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