Mechanical compression creates a quiescent muscle stem cell niche

Tissue stem cell niches are regulated by their mechanical environment, notably the extracellular matrix (ECM). Skeletal muscles consist of bundled myofibers for force transmission. Within this macroscopic architecture, quiescent Pax7-expressing (Pax7 + ) muscle stem cells (MuSCs) are compressed betw...

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Bibliographic Details
Published in:Communications biology 2023-01, Vol.6 (1), p.43-43, Article 43
Main Authors: Tao, Jiaxiang, Choudhury, Mohammad Ikbal, Maity, Debonil, Kim, Taeki, Sun, Sean X., Fan, Chen-Ming
Format: Article
Language:English
Subjects:
631/532
631/57
Biology
Biomedical and Life Sciences
Cell cycle
Compression
Extracellular matrix
Gene regulation
Life Sciences
Mathematical models
Muscle contraction
Muscle, Skeletal - metabolism
Notch1 protein
Satellite Cells, Skeletal Muscle - metabolism
Skeletal muscle
Stem Cell Niche
Stem Cells
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Summary:Tissue stem cell niches are regulated by their mechanical environment, notably the extracellular matrix (ECM). Skeletal muscles consist of bundled myofibers for force transmission. Within this macroscopic architecture, quiescent Pax7-expressing (Pax7 + ) muscle stem cells (MuSCs) are compressed between ECM basally and myofiber apically. Muscle injury causes MuSCs to lose apical compression from the myofiber and re-enter the cell cycle for regeneration. While ECM elasticities have been shown to affect MuSC’s renewal, the significance of apical compression remains unknown. To investigate the role of apical compression, we simulate the MuSCs’ in vivo mechanical environment by applying physical compression to MuSCs’ apical surface. We demonstrate that compression drives activated MuSCs back to a quiescent stem cell state, regardless of basal elasticities and chemistries. By mathematical modeling and cell tension manipulation, we conclude that low overall tension combined with high axial tension generated by compression leads to MuSCs’ stemness and quiescence. Unexpectedly, we discovered that apical compression results in up-regulation of Notch downstream genes, accompanied by the increased levels of nuclear Notch1&3 in a Delta ligand (Dll) and ADAM10/17 independent manner. Our results fill a knowledge gap on the role of apical compression for MuSC fate and have implications to stem cells in other tissues. Mechanical compression drives activated muscle stem cells (MuSCs) into a quiescent stem cell state providing insight into MuSC activity during injury-regeneration cycles.
ISSN:2399-3642
2399-3642
DOI:10.1038/s42003-023-04411-2