Metabolic Changes during In Vivo Maturation of PSC-Derived Skeletal Myogenic Progenitors

In vitro-generated pluripotent stem cell (PSC)-derived Pax3-induced (iPax3) myogenic progenitors display an embryonic transcriptional signature, but upon engraftment, the profile of re-isolated iPax3 donor-derived satellite cells changes toward similarity with postnatal satellite cells, suggesting t...

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Main Authors: Phablo Abreu, Bayardo I. Garay, Travis Nemkov, Aline M. S. Yamashita, Rita C. R. Perlingeiro
Format: Article
Language:English
Published: MDPI AG 2023-12-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/13/1/76
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author Phablo Abreu
Bayardo I. Garay
Travis Nemkov
Aline M. S. Yamashita
Rita C. R. Perlingeiro
author_facet Phablo Abreu
Bayardo I. Garay
Travis Nemkov
Aline M. S. Yamashita
Rita C. R. Perlingeiro
author_sort Phablo Abreu
collection DOAJ
description In vitro-generated pluripotent stem cell (PSC)-derived Pax3-induced (iPax3) myogenic progenitors display an embryonic transcriptional signature, but upon engraftment, the profile of re-isolated iPax3 donor-derived satellite cells changes toward similarity with postnatal satellite cells, suggesting that engrafted PSC-derived myogenic cells remodel their transcriptional signature upon interaction within the adult muscle environment. Here, we show that engrafted myogenic progenitors also remodel their metabolic state. Assessment of oxygen consumption revealed that exposure to the adult muscle environment promotes overt changes in mitochondrial bioenergetics, as shown by the substantial suppression of energy requirements in re-isolated iPax3 donor-derived satellite cells compared to their in vitro-generated progenitors. Mass spectrometry-based metabolomic profiling further confirmed the relationship of engrafted iPax3 donor-derived cells to adult satellite cells. The fact that in vitro-generated myogenic progenitors remodel their bioenergetic signature upon in vivo exposure to the adult muscle environment may have important implications for therapeutic applications.
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spelling doaj.art-033f315218224500ae4233e243c2c9062024-01-10T14:53:26ZengMDPI AGCells2073-44092023-12-011317610.3390/cells13010076Metabolic Changes during In Vivo Maturation of PSC-Derived Skeletal Myogenic ProgenitorsPhablo Abreu0Bayardo I. Garay1Travis Nemkov2Aline M. S. Yamashita3Rita C. R. Perlingeiro4Lillehei Heart Institute, Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USALillehei Heart Institute, Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USADepartment of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USALillehei Heart Institute, Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USALillehei Heart Institute, Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USAIn vitro-generated pluripotent stem cell (PSC)-derived Pax3-induced (iPax3) myogenic progenitors display an embryonic transcriptional signature, but upon engraftment, the profile of re-isolated iPax3 donor-derived satellite cells changes toward similarity with postnatal satellite cells, suggesting that engrafted PSC-derived myogenic cells remodel their transcriptional signature upon interaction within the adult muscle environment. Here, we show that engrafted myogenic progenitors also remodel their metabolic state. Assessment of oxygen consumption revealed that exposure to the adult muscle environment promotes overt changes in mitochondrial bioenergetics, as shown by the substantial suppression of energy requirements in re-isolated iPax3 donor-derived satellite cells compared to their in vitro-generated progenitors. Mass spectrometry-based metabolomic profiling further confirmed the relationship of engrafted iPax3 donor-derived cells to adult satellite cells. The fact that in vitro-generated myogenic progenitors remodel their bioenergetic signature upon in vivo exposure to the adult muscle environment may have important implications for therapeutic applications.https://www.mdpi.com/2073-4409/13/1/76pluripotent stem cellsmyogenic progenitorsmetabolismin vitroin vivosatellite cells
spellingShingle Phablo Abreu
Bayardo I. Garay
Travis Nemkov
Aline M. S. Yamashita
Rita C. R. Perlingeiro
Metabolic Changes during In Vivo Maturation of PSC-Derived Skeletal Myogenic Progenitors
Cells
pluripotent stem cells
myogenic progenitors
metabolism
in vitro
in vivo
satellite cells
title Metabolic Changes during In Vivo Maturation of PSC-Derived Skeletal Myogenic Progenitors
title_full Metabolic Changes during In Vivo Maturation of PSC-Derived Skeletal Myogenic Progenitors
title_fullStr Metabolic Changes during In Vivo Maturation of PSC-Derived Skeletal Myogenic Progenitors
title_full_unstemmed Metabolic Changes during In Vivo Maturation of PSC-Derived Skeletal Myogenic Progenitors
title_short Metabolic Changes during In Vivo Maturation of PSC-Derived Skeletal Myogenic Progenitors
title_sort metabolic changes during in vivo maturation of psc derived skeletal myogenic progenitors
topic pluripotent stem cells
myogenic progenitors
metabolism
in vitro
in vivo
satellite cells
url https://www.mdpi.com/2073-4409/13/1/76
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AT bayardoigaray metabolicchangesduringinvivomaturationofpscderivedskeletalmyogenicprogenitors
AT travisnemkov metabolicchangesduringinvivomaturationofpscderivedskeletalmyogenicprogenitors
AT alinemsyamashita metabolicchangesduringinvivomaturationofpscderivedskeletalmyogenicprogenitors
AT ritacrperlingeiro metabolicchangesduringinvivomaturationofpscderivedskeletalmyogenicprogenitors