Three-dimensional niche stiffness synergizes with Wnt7a to modulate the extent of satellite cell symmetric self-renewal divisions
File(s)mbc.e20-01-0078.pdf (1.23 MB)
Published version
Author(s)
Type
Journal Article
Abstract
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 non-canonical 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.
Date Issued
2020-06-03
Date Acceptance
2020-05-26
Citation
Molecular Biology of the Cell, 2020, 31 (16), pp.1-11
ISSN
1059-1524
Publisher
American Society for Cell Biology (ASCB)
Start Page
1
End Page
11
Journal / Book Title
Molecular Biology of the Cell
Volume
31
Issue
16
Copyright Statement
© 2020 Moyle et al. 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 (http://creativecommons.org/licenses/by-nc-sa/3.0).
Identifier
https://www.molbiolcell.org/doi/10.1091/mbc.E20-01-0078
Subjects
Developmental Biology
06 Biological Sciences
11 Medical and Health Sciences
Publication Status
Published
Date Publish Online
2020-06-03