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Tubastatin A maintains adult skeletal muscle stem cells in a quiescent state ex vivo and improves their engraftment ability in vivo

Adult skeletal muscle stem cells (MuSCs) are important for muscle regeneration and constitute a potential source of cell therapy. However, upon isolation, MuSCs rapidly exit quiescence and lose transplantation potency. Maintenance of the quiescent state in vitro preserves MuSC transplantation effici...

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Autores principales: Arjona, Marina, Goshayeshi, Armon, Rodriguez-Mateo, Cristina, Brett, Jamie O., Both, Pieter, Ishak, Heather, Rando, Thomas A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8758944/
https://www.ncbi.nlm.nih.gov/pubmed/35021050
http://dx.doi.org/10.1016/j.stemcr.2021.11.012
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author Arjona, Marina
Goshayeshi, Armon
Rodriguez-Mateo, Cristina
Brett, Jamie O.
Both, Pieter
Ishak, Heather
Rando, Thomas A.
author_facet Arjona, Marina
Goshayeshi, Armon
Rodriguez-Mateo, Cristina
Brett, Jamie O.
Both, Pieter
Ishak, Heather
Rando, Thomas A.
author_sort Arjona, Marina
collection PubMed
description Adult skeletal muscle stem cells (MuSCs) are important for muscle regeneration and constitute a potential source of cell therapy. However, upon isolation, MuSCs rapidly exit quiescence and lose transplantation potency. Maintenance of the quiescent state in vitro preserves MuSC transplantation efficiency and provides an opportunity to study the biology of quiescence. Here we show that Tubastatin A (TubA), an Hdac6 inhibitor, prevents primary cilium resorption, maintains quiescence, and enhances MuSC survival ex vivo. Phenotypic characterization and transcriptomic analysis of TubA-treated cells revealed that TubA maintains most of the biological features and molecular signatures of quiescence. Furthermore, TubA-treated MuSCs showed improved engraftment ability upon transplantation. TubA also induced a return to quiescence and improved engraftment of cycling MuSCs, revealing a potentially expanded application for MuSC therapeutics. Altogether, these studies demonstrate the ability of TubA to maintain MuSC quiescence ex vivo and to enhance the therapeutic potential of MuSCs and their progeny.
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spelling pubmed-87589442022-01-19 Tubastatin A maintains adult skeletal muscle stem cells in a quiescent state ex vivo and improves their engraftment ability in vivo Arjona, Marina Goshayeshi, Armon Rodriguez-Mateo, Cristina Brett, Jamie O. Both, Pieter Ishak, Heather Rando, Thomas A. Stem Cell Reports Article Adult skeletal muscle stem cells (MuSCs) are important for muscle regeneration and constitute a potential source of cell therapy. However, upon isolation, MuSCs rapidly exit quiescence and lose transplantation potency. Maintenance of the quiescent state in vitro preserves MuSC transplantation efficiency and provides an opportunity to study the biology of quiescence. Here we show that Tubastatin A (TubA), an Hdac6 inhibitor, prevents primary cilium resorption, maintains quiescence, and enhances MuSC survival ex vivo. Phenotypic characterization and transcriptomic analysis of TubA-treated cells revealed that TubA maintains most of the biological features and molecular signatures of quiescence. Furthermore, TubA-treated MuSCs showed improved engraftment ability upon transplantation. TubA also induced a return to quiescence and improved engraftment of cycling MuSCs, revealing a potentially expanded application for MuSC therapeutics. Altogether, these studies demonstrate the ability of TubA to maintain MuSC quiescence ex vivo and to enhance the therapeutic potential of MuSCs and their progeny. Elsevier 2022-01-11 /pmc/articles/PMC8758944/ /pubmed/35021050 http://dx.doi.org/10.1016/j.stemcr.2021.11.012 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Arjona, Marina
Goshayeshi, Armon
Rodriguez-Mateo, Cristina
Brett, Jamie O.
Both, Pieter
Ishak, Heather
Rando, Thomas A.
Tubastatin A maintains adult skeletal muscle stem cells in a quiescent state ex vivo and improves their engraftment ability in vivo
title Tubastatin A maintains adult skeletal muscle stem cells in a quiescent state ex vivo and improves their engraftment ability in vivo
title_full Tubastatin A maintains adult skeletal muscle stem cells in a quiescent state ex vivo and improves their engraftment ability in vivo
title_fullStr Tubastatin A maintains adult skeletal muscle stem cells in a quiescent state ex vivo and improves their engraftment ability in vivo
title_full_unstemmed Tubastatin A maintains adult skeletal muscle stem cells in a quiescent state ex vivo and improves their engraftment ability in vivo
title_short Tubastatin A maintains adult skeletal muscle stem cells in a quiescent state ex vivo and improves their engraftment ability in vivo
title_sort tubastatin a maintains adult skeletal muscle stem cells in a quiescent state ex vivo and improves their engraftment ability in vivo
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8758944/
https://www.ncbi.nlm.nih.gov/pubmed/35021050
http://dx.doi.org/10.1016/j.stemcr.2021.11.012
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