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J Neurosci. 2016 Jan 20;36(3):806-13. doi: 10.1523/JNEUROSCI.2873-15.2016.

Mechanostimulation Promotes Nuclear and Epigenetic Changes in Oligodendrocytes.

Author information

1
Department of Neuroscience, Graduate School of Biological Sciences.
2
Department of Neuroscience.
3
Department of Neurology and Program in Neurosciences, University of California, San Francisco, San Francisco, California 94145-0339.
4
Cardiovascular Research Center, and.
5
Department of Neuroscience, Department of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York 10029-5674, and patrizia.casaccia@mssm.edu.

Abstract

Oligodendrocyte progenitors respond to biophysical or mechanical signals, and it has been reported that mechanostimulation modulates cell proliferation, migration, and differentiation. Here we report the effect of three mechanical stimuli on mouse oligodendrocyte progenitor differentiation and identify the molecular components of the linker of nucleoskeleton and cytoskeleton (LINC) complex (i.e., SYNE1) as transducers of mechanical signals to the nucleus, where they modulate the deposition of repressive histone marks and heterochromatin formation. The expression levels of LINC components increased during progenitor differentiation and silencing the Syne1 gene resulted in aberrant histone marks deposition, chromatin reorganization and impaired myelination. We conclude that spatial constraints, via the actin cytoskeleton and LINC complex, mediate nuclear changes in oligodendrocyte progenitors that favor a default pathway of differentiation. Significance statement: It is recognized that oligodendrocyte progenitors are mechanosensitive cells. However, the molecular mechanisms translating mechanical stimuli into oligodendrocyte differentiation remain elusive. This study identifies components of the mechanotransduction pathway in the oligodendrocyte lineage.

KEYWORDS:

chromatin; cytoskeleton; histone; myelin; nucleus

PMID:
26791211
PMCID:
PMC4719016
DOI:
10.1523/JNEUROSCI.2873-15.2016
[Indexed for MEDLINE]
Free PMC Article

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