Screening identifies small molecules that enhance the maturation of human pluripotent stem cell-derived myotubes.

Autor:	Selvaraj S; Lillehei Heart Institute, Department of Medicine, University of Minnesota, Minneapolis, United States., Mondragon-Gonzalez R; Lillehei Heart Institute, Department of Medicine, University of Minnesota, Minneapolis, United States.; Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados del IPN (CINVESTAV-IPN), Ciudad de México, Mexico., Xu B; Department of Biomedical Engineering, University of Minnesota, Minneapolis, United States., Magli A; Lillehei Heart Institute, Department of Medicine, University of Minnesota, Minneapolis, United States.; Stem Cell Institute, University of Minnesota, Minneapolis, United States., Kim H; Lillehei Heart Institute, Department of Medicine, University of Minnesota, Minneapolis, United States., Lainé J; Département de Physiologie, Sorbonne Universités, Faculté de Médecine site Pitié-Salpêtrière, Paris, France., Kiley J; Lillehei Heart Institute, Department of Medicine, University of Minnesota, Minneapolis, United States., Mckee H; Lillehei Heart Institute, Department of Medicine, University of Minnesota, Minneapolis, United States., Rinaldi F; Stem Cell Department, Bio-Techne, Minneapolis, United States., Aho J; Stem Cell Department, Bio-Techne, Minneapolis, United States., Tabti N; Département de Physiologie, Sorbonne Universités, Faculté de Médecine site Pitié-Salpêtrière, Paris, France., Shen W; Lillehei Heart Institute, Department of Medicine, University of Minnesota, Minneapolis, United States.; Department of Biomedical Engineering, University of Minnesota, Minneapolis, United States.; Stem Cell Institute, University of Minnesota, Minneapolis, United States., Perlingeiro RC; Lillehei Heart Institute, Department of Medicine, University of Minnesota, Minneapolis, United States.; Stem Cell Institute, University of Minnesota, Minneapolis, United States.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2019 Nov 11; Vol. 8. Date of Electronic Publication: 2019 Nov 11.
DOI:	10.7554/eLife.47970
Abstrakt:	Targeted differentiation of pluripotent stem (PS) cells into myotubes enables in vitro disease modeling of skeletal muscle diseases. Although various protocols achieve myogenic differentiation in vitro, resulting myotubes typically display an embryonic identity. This is a major hurdle for accurately recapitulating disease phenotypes in vitro, as disease commonly manifests at later stages of development. To address this problem, we identified four factors from a small molecule screen whose combinatorial treatment resulted in myotubes with enhanced maturation, as shown by the expression profile of myosin heavy chain isoforms, as well as the upregulation of genes related with muscle contractile function. These molecular changes were confirmed by global chromatin accessibility and transcriptome studies. Importantly, we also observed this maturation in three-dimensional muscle constructs, which displayed improved in vitro contractile force generation in response to electrical stimulus. Thus, we established a model for in vitro muscle maturation from PS cells. Competing Interests: SS, RM, BX, AM, HK, JL, JK, HM, NT, WS, RP No competing interests declared, FR, JA is affiliated with Bio-Techne. The author has no financial interests to declare. (© 2019, Selvaraj et al.)
Databáze:	MEDLINE
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