Mechanostimulation Promotes Nuclear and Epigenetic Changes in Oligodendrocytes

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