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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
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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. |
format | Online Article Text |
id | pubmed-8758944 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
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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