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Three-dimensional niche stiffness synergizes with Wnt7a to modulate the extent of satellite cell symmetric self-renewal divisions

Satellite cells (SCs), the resident adult stem cells of skeletal muscle, are required for tissue repair throughout life. While many signaling pathways are known to control SC self-renewal, less is known about the mechanisms underlying the spatiotemporal control of self-renewal during skeletal muscle...

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Autores principales: Moyle, Louise A., Cheng, Richard Y., Liu, Haijiao, Davoudi, Sadegh, Ferreira, Silvia A., Nissar, Aliyah A., Sun, Yu, Gentleman, Eileen, Simmons, Craig A., Gilbert, Penney M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521850/
https://www.ncbi.nlm.nih.gov/pubmed/32491970
http://dx.doi.org/10.1091/mbc.E20-01-0078
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author Moyle, Louise A.
Cheng, Richard Y.
Liu, Haijiao
Davoudi, Sadegh
Ferreira, Silvia A.
Nissar, Aliyah A.
Sun, Yu
Gentleman, Eileen
Simmons, Craig A.
Gilbert, Penney M.
author_facet Moyle, Louise A.
Cheng, Richard Y.
Liu, Haijiao
Davoudi, Sadegh
Ferreira, Silvia A.
Nissar, Aliyah A.
Sun, Yu
Gentleman, Eileen
Simmons, Craig A.
Gilbert, Penney M.
author_sort Moyle, Louise A.
collection PubMed
description Satellite cells (SCs), the resident adult stem cells of skeletal muscle, are required for tissue repair throughout life. While many signaling pathways are known to control SC self-renewal, less is known about the mechanisms underlying the spatiotemporal control of self-renewal during skeletal muscle repair. Here, we measured biomechanical changes that accompany skeletal muscle regeneration and determined the implications on SC fate. Using atomic force microscopy, we quantified a 2.9-fold stiffening of the SC niche at time-points associated with planar-oriented symmetric self-renewal divisions. Immunohistochemical analysis confirms increased extracellular matrix deposition within the basal lamina. To test whether three-dimensional (3D) niche stiffness can alter SC behavior or fate, we embedded isolated SC-associated muscle fibers within biochemically inert agarose gels tuned to mimic native tissue stiffness. Time-lapse microscopy revealed that a stiff 3D niche significantly increased the proportion of planar-oriented divisions, without effecting SC viability, fibronectin deposition, or fate change. We then found that 3D niche stiffness synergizes with WNT7a, a biomolecule shown to control SC symmetric self-renewal divisions via the noncanonical WNT/planar cell polarity pathway, to modify stem cell pool expansion. Our results provide new insights into the role of 3D niche biomechanics in regulating SC fate choice.
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spelling pubmed-75218502020-10-06 Three-dimensional niche stiffness synergizes with Wnt7a to modulate the extent of satellite cell symmetric self-renewal divisions Moyle, Louise A. Cheng, Richard Y. Liu, Haijiao Davoudi, Sadegh Ferreira, Silvia A. Nissar, Aliyah A. Sun, Yu Gentleman, Eileen Simmons, Craig A. Gilbert, Penney M. Mol Biol Cell Articles Satellite cells (SCs), the resident adult stem cells of skeletal muscle, are required for tissue repair throughout life. While many signaling pathways are known to control SC self-renewal, less is known about the mechanisms underlying the spatiotemporal control of self-renewal during skeletal muscle repair. Here, we measured biomechanical changes that accompany skeletal muscle regeneration and determined the implications on SC fate. Using atomic force microscopy, we quantified a 2.9-fold stiffening of the SC niche at time-points associated with planar-oriented symmetric self-renewal divisions. Immunohistochemical analysis confirms increased extracellular matrix deposition within the basal lamina. To test whether three-dimensional (3D) niche stiffness can alter SC behavior or fate, we embedded isolated SC-associated muscle fibers within biochemically inert agarose gels tuned to mimic native tissue stiffness. Time-lapse microscopy revealed that a stiff 3D niche significantly increased the proportion of planar-oriented divisions, without effecting SC viability, fibronectin deposition, or fate change. We then found that 3D niche stiffness synergizes with WNT7a, a biomolecule shown to control SC symmetric self-renewal divisions via the noncanonical WNT/planar cell polarity pathway, to modify stem cell pool expansion. Our results provide new insights into the role of 3D niche biomechanics in regulating SC fate choice. The American Society for Cell Biology 2020-07-21 /pmc/articles/PMC7521850/ /pubmed/32491970 http://dx.doi.org/10.1091/mbc.E20-01-0078 Text en © 2020 Moyle et al. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. http://creativecommons.org/licenses/by-nc-sa/3.0 This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License.
spellingShingle Articles
Moyle, Louise A.
Cheng, Richard Y.
Liu, Haijiao
Davoudi, Sadegh
Ferreira, Silvia A.
Nissar, Aliyah A.
Sun, Yu
Gentleman, Eileen
Simmons, Craig A.
Gilbert, Penney M.
Three-dimensional niche stiffness synergizes with Wnt7a to modulate the extent of satellite cell symmetric self-renewal divisions
title Three-dimensional niche stiffness synergizes with Wnt7a to modulate the extent of satellite cell symmetric self-renewal divisions
title_full Three-dimensional niche stiffness synergizes with Wnt7a to modulate the extent of satellite cell symmetric self-renewal divisions
title_fullStr Three-dimensional niche stiffness synergizes with Wnt7a to modulate the extent of satellite cell symmetric self-renewal divisions
title_full_unstemmed Three-dimensional niche stiffness synergizes with Wnt7a to modulate the extent of satellite cell symmetric self-renewal divisions
title_short Three-dimensional niche stiffness synergizes with Wnt7a to modulate the extent of satellite cell symmetric self-renewal divisions
title_sort three-dimensional niche stiffness synergizes with wnt7a to modulate the extent of satellite cell symmetric self-renewal divisions
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521850/
https://www.ncbi.nlm.nih.gov/pubmed/32491970
http://dx.doi.org/10.1091/mbc.E20-01-0078
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