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Piezo1 regulates the regenerative capacity of skeletal muscles via orchestration of stem cell morphological states
Muscle stem cells (MuSCs) are essential for tissue homeostasis and regeneration, but the potential contribution of MuSC morphology to in vivo function remains unknown. Here, we demonstrate that quiescent MuSCs are morphologically heterogeneous and exhibit different patterns of cellular protrusions....
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8932657/ https://www.ncbi.nlm.nih.gov/pubmed/35302846 http://dx.doi.org/10.1126/sciadv.abn0485 |
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author | Ma, Nuoying Chen, Delia Lee, Ji-Hyung Kuri, Paola Hernandez, Edward Blake Kocan, Jacob Mahmood, Hamd Tichy, Elisia D. Rompolas, Panteleimon Mourkioti, Foteini |
author_facet | Ma, Nuoying Chen, Delia Lee, Ji-Hyung Kuri, Paola Hernandez, Edward Blake Kocan, Jacob Mahmood, Hamd Tichy, Elisia D. Rompolas, Panteleimon Mourkioti, Foteini |
author_sort | Ma, Nuoying |
collection | PubMed |
description | Muscle stem cells (MuSCs) are essential for tissue homeostasis and regeneration, but the potential contribution of MuSC morphology to in vivo function remains unknown. Here, we demonstrate that quiescent MuSCs are morphologically heterogeneous and exhibit different patterns of cellular protrusions. We classified quiescent MuSCs into three functionally distinct stem cell states: responsive, intermediate, and sensory. We demonstrate that the shift between different stem cell states promotes regeneration and is regulated by the sensing protein Piezo1. Pharmacological activation of Piezo1 is sufficient to prime MuSCs toward more responsive cells. Piezo1 deletion in MuSCs shifts the distribution toward less responsive cells, mimicking the disease phenotype we find in dystrophic muscles. We further demonstrate that Piezo1 reactivation ameliorates the MuSC morphological and regenerative defects of dystrophic muscles. These findings advance our fundamental understanding of how stem cells respond to injury and identify Piezo1 as a key regulator for adjusting stem cell states essential for regeneration. |
format | Online Article Text |
id | pubmed-8932657 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-89326572022-03-31 Piezo1 regulates the regenerative capacity of skeletal muscles via orchestration of stem cell morphological states Ma, Nuoying Chen, Delia Lee, Ji-Hyung Kuri, Paola Hernandez, Edward Blake Kocan, Jacob Mahmood, Hamd Tichy, Elisia D. Rompolas, Panteleimon Mourkioti, Foteini Sci Adv Biomedicine and Life Sciences Muscle stem cells (MuSCs) are essential for tissue homeostasis and regeneration, but the potential contribution of MuSC morphology to in vivo function remains unknown. Here, we demonstrate that quiescent MuSCs are morphologically heterogeneous and exhibit different patterns of cellular protrusions. We classified quiescent MuSCs into three functionally distinct stem cell states: responsive, intermediate, and sensory. We demonstrate that the shift between different stem cell states promotes regeneration and is regulated by the sensing protein Piezo1. Pharmacological activation of Piezo1 is sufficient to prime MuSCs toward more responsive cells. Piezo1 deletion in MuSCs shifts the distribution toward less responsive cells, mimicking the disease phenotype we find in dystrophic muscles. We further demonstrate that Piezo1 reactivation ameliorates the MuSC morphological and regenerative defects of dystrophic muscles. These findings advance our fundamental understanding of how stem cells respond to injury and identify Piezo1 as a key regulator for adjusting stem cell states essential for regeneration. American Association for the Advancement of Science 2022-03-18 /pmc/articles/PMC8932657/ /pubmed/35302846 http://dx.doi.org/10.1126/sciadv.abn0485 Text en Copyright © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
spellingShingle | Biomedicine and Life Sciences Ma, Nuoying Chen, Delia Lee, Ji-Hyung Kuri, Paola Hernandez, Edward Blake Kocan, Jacob Mahmood, Hamd Tichy, Elisia D. Rompolas, Panteleimon Mourkioti, Foteini Piezo1 regulates the regenerative capacity of skeletal muscles via orchestration of stem cell morphological states |
title | Piezo1 regulates the regenerative capacity of skeletal muscles via orchestration of stem cell morphological states |
title_full | Piezo1 regulates the regenerative capacity of skeletal muscles via orchestration of stem cell morphological states |
title_fullStr | Piezo1 regulates the regenerative capacity of skeletal muscles via orchestration of stem cell morphological states |
title_full_unstemmed | Piezo1 regulates the regenerative capacity of skeletal muscles via orchestration of stem cell morphological states |
title_short | Piezo1 regulates the regenerative capacity of skeletal muscles via orchestration of stem cell morphological states |
title_sort | piezo1 regulates the regenerative capacity of skeletal muscles via orchestration of stem cell morphological states |
topic | Biomedicine and Life Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8932657/ https://www.ncbi.nlm.nih.gov/pubmed/35302846 http://dx.doi.org/10.1126/sciadv.abn0485 |
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