Differentiation alters stem cell nuclear architecture, mechanics, and mechano-sensitivity
- Perelman School of Medicine, University of Pennsylvania, United States
- Queen Mary University of London, United Kingdom
- Harvard University, United States
- Boston University, United States
Abstract
Mesenchymal stem cell (MSC) differentiation is mediated by soluble and physical cues. In this study, we investigated differentiation induced transformations in MSC cellular and nuclear biophysical properties and queried their role in mechanosensation. Our data show that nuclei in differentiated bovine and human MSCs stiffen and become resistant to deformation. This attenuated nuclear deformation was governed by restructuring of Lamin A/C and increased heterochromatin content. This change in nuclear stiffness sensitized MSCs to mechanical loading induced calcium signaling and differentiated marker expression. This sensitization was reversed when the 'stiff' differentiated nucleus was softened, and was enhanced when the 'soft' undifferentiated nucleus was stiffened through pharmacologic treatment. Interestingly, dynamic loading of undifferentiated MSCs, in the absence of soluble differentiation factors, stiffened and condensed the nucleus, and increased mechanosensitivity more rapidly than soluble factors. These data suggest that the nucleus acts as a mechanostat to modulate cellular mechanosensation during differentiation.
Article and author information
Author details
Funding
National Institutes of Health
- Su-Jin Heo
- Tristan P Driscoll
- Nandan L Nerurkar
- Brendon M Baker
- Michael T Yang
- Christopher S Chen
- Robert L Mauck
Human Frontiers in Science Program
- Su-Jin Heo
- Tristan P Driscoll
- Stephen D Thorpe
- David A Lee
- Robert L Mauck
The Penn Center for Musculoskeletal Disorders
- Su-Jin Heo
- Tristan P Driscoll
- Robert L Mauck
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Todd McDevitt, Gladstone Institutes, United States
Version history
- Received: June 3, 2016
- Accepted: November 29, 2016
- Accepted Manuscript published: November 30, 2016 (version 1)
- Version of Record published: December 9, 2016 (version 2)
Copyright
© 2016, Heo et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Differentiation alters stem cell nuclear architecture, mechanics, and mechano-sensitivity
eLife 5:e18207.
https://doi.org/10.7554/eLife.18207
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