title: Mechanostimulation Promotes Nuclear and Epigenetic Changes in Oligodendrocytes.
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.
authors.affiliation: Department of Neuroscience, Graduate School of Biological Sciences.
authors.forename: Marylens
authors.initials: M
authors.lastname: Hernandez
authors.affiliation: Department of Neuroscience.
authors.forename: Julia
authors.identifier: http://orcid.org/0000-0001-5976-9592
authors.initials: J
authors.lastname: Patzig
authors.affiliation: Department of Neurology and Program in Neurosciences, University of California, San Francisco, San Francisco, California 94145-0339.
authors.forename: Sonia R
authors.identifier: http://orcid.org/0000-0002-7766-5743
authors.initials: SR
authors.lastname: Mayoral
authors.affiliation: Cardiovascular Research Center, and.
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Costa
authors.affiliation: Department of Neurology and Program in Neurosciences, University of California, San Francisco, San Francisco, California 94145-0339.
authors.forename: Jonah R
authors.identifier: http://orcid.org/0000-0002-2176-1242
authors.initials: JR
authors.lastname: Chan
authors.affiliation: 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.
authors.forename: Patrizia
authors.identifier: http://orcid.org/0000-0002-4785-9264
authors.initials: P
authors.lastname: Casaccia
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D003598:Cytoskeletal Proteins; D044127:Epigenesis, Genetic / Q000502:physiology*; D005260:Female; D008297:Male; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics; D009836:Oligodendroglia / Q000502:physiology*
chemical_list: D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C485901:Syne1 protein, mouse
keywords: chromatin; cytoskeleton; histone; myelin; nucleus