Three-dimensional niche stiffness synergizes with Wnt7a to modulate the extent of satellite cell symmetric self-renewal divisions.
Details
Serval ID
serval:BIB_6367C4BDCA7B
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Three-dimensional niche stiffness synergizes with Wnt7a to modulate the extent of satellite cell symmetric self-renewal divisions.
Journal
Molecular biology of the cell
ISSN
1939-4586 (Electronic)
ISSN-L
1059-1524
Publication state
Published
Issued date
21/07/2020
Peer-reviewed
Oui
Volume
31
Number
16
Pages
1703-1713
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
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 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.
Keywords
Adult Stem Cells, Animals, Cell Differentiation/physiology, Cell Proliferation/physiology, Elasticity/physiology, Extracellular Matrix/metabolism, Female, Fibronectins/genetics, Fibronectins/metabolism, Hardness/physiology, Humans, Mice, Mice, Inbred C57BL, Mice, Transgenic, Microscopy, Atomic Force/methods, Muscle Fibers, Skeletal, Muscle, Skeletal/metabolism, Muscle, Skeletal/physiology, Regeneration/physiology, Satellite Cells, Skeletal Muscle/metabolism, Satellite Cells, Skeletal Muscle/physiology, Signal Transduction/physiology, Stem Cell Niche/physiology, Wnt Proteins/genetics, Wnt Proteins/metabolism, Wound Healing/physiology
Pubmed
Web of science
Open Access
Yes
Create date
12/01/2024 10:14
Last modification date
13/01/2024 7:10