Mechanical Strain Promotes Oligodendrocyte Differentiation by Global Changes of Gene Expression
Differentiation of oligodendrocyte progenitor cells (OPC) to oligodendrocytes and subsequent axon myelination are critical steps in vertebrate central nervous system (CNS) development and regeneration. Growing evidence supports the significance of mechanical factors in oligodendrocyte biology. Here,...
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doaj-ee7455fb847c4337ba68b307620702672020-11-24T23:58:11ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022017-04-011110.3389/fncel.2017.00093251525Mechanical Strain Promotes Oligodendrocyte Differentiation by Global Changes of Gene ExpressionKrystyn J. Van Vliet0Krystyn J. Van Vliet1Krystyn J. Van Vliet2Anna Jagielska3Alexis L. Lowe4Ekta Makhija5Liliana Wroblewska6Jochen Guck7Robin J. M. Franklin8G. V. Shivashankar9Department of Materials Science and Engineering, Massachusetts Institute of TechnologyCambridge, MA, USADepartment of Biological Engineering, Massachusetts Institute of TechnologyCambridge, MA, USABioSystems and Micromechanics Inter-Disciplinary Research Group, Singapore-MIT Alliance for Research and TechnologySingapore, SingaporeDepartment of Materials Science and Engineering, Massachusetts Institute of TechnologyCambridge, MA, USADepartment of Neuroscience, Wellesley CollegeWellesley, MA, USAMechanobiology Institute, National University of SingaporeSingapore, SingaporeDepartment of Biological Engineering, Massachusetts Institute of TechnologyCambridge, MA, USABiotechnology Center, Technische Universität DresdenDresden, GermanyWellcome Trust - Medical Research Council Cambridge Stem Cell Institute and Department of Clinical Neurosciences, University of CambridgeCambridge, UKMechanobiology Institute, National University of SingaporeSingapore, SingaporeDifferentiation of oligodendrocyte progenitor cells (OPC) to oligodendrocytes and subsequent axon myelination are critical steps in vertebrate central nervous system (CNS) development and regeneration. Growing evidence supports the significance of mechanical factors in oligodendrocyte biology. Here, we explore the effect of mechanical strains within physiological range on OPC proliferation and differentiation, and strain-associated changes in chromatin structure, epigenetics, and gene expression. Sustained tensile strain of 10–15% inhibited OPC proliferation and promoted differentiation into oligodendrocytes. This response to strain required specific interactions of OPCs with extracellular matrix ligands. Applied strain induced changes in nuclear shape, chromatin organization, and resulted in enhanced histone deacetylation, consistent with increased oligodendrocyte differentiation. This response was concurrent with increased mRNA levels of the epigenetic modifier histone deacetylase Hdac11. Inhibition of HDAC proteins eliminated the strain-mediated increase of OPC differentiation, demonstrating a role of HDACs in mechanotransduction of strain to chromatin. RNA sequencing revealed global changes in gene expression associated with strain. Specifically, expression of multiple genes associated with oligodendrocyte differentiation and axon-oligodendrocyte interactions was increased, including cell surface ligands (Ncam, ephrins), cyto- and nucleo-skeleton genes (Fyn, actinins, myosin, nesprin, Sun1), transcription factors (Sox10, Zfp191, Nkx2.2), and myelin genes (Cnp, Plp, Mag). These findings show how mechanical strain can be transmitted to the nucleus to promote oligodendrocyte differentiation, and identify the global landscape of signaling pathways involved in mechanotransduction. These data provide a source of potential new therapeutic avenues to enhance OPC differentiation in vivo.http://journal.frontiersin.org/article/10.3389/fncel.2017.00093/fulloligodendrocytesoligodendrocyte precursor cell (OPC)oligodendrocyte differentiationmechanical strainmultiple sclerosis (MS)mechanotransduction |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Krystyn J. Van Vliet Krystyn J. Van Vliet Krystyn J. Van Vliet Anna Jagielska Alexis L. Lowe Ekta Makhija Liliana Wroblewska Jochen Guck Robin J. M. Franklin G. V. Shivashankar |
spellingShingle |
Krystyn J. Van Vliet Krystyn J. Van Vliet Krystyn J. Van Vliet Anna Jagielska Alexis L. Lowe Ekta Makhija Liliana Wroblewska Jochen Guck Robin J. M. Franklin G. V. Shivashankar Mechanical Strain Promotes Oligodendrocyte Differentiation by Global Changes of Gene Expression Frontiers in Cellular Neuroscience oligodendrocytes oligodendrocyte precursor cell (OPC) oligodendrocyte differentiation mechanical strain multiple sclerosis (MS) mechanotransduction |
author_facet |
Krystyn J. Van Vliet Krystyn J. Van Vliet Krystyn J. Van Vliet Anna Jagielska Alexis L. Lowe Ekta Makhija Liliana Wroblewska Jochen Guck Robin J. M. Franklin G. V. Shivashankar |
author_sort |
Krystyn J. Van Vliet |
title |
Mechanical Strain Promotes Oligodendrocyte Differentiation by Global Changes of Gene Expression |
title_short |
Mechanical Strain Promotes Oligodendrocyte Differentiation by Global Changes of Gene Expression |
title_full |
Mechanical Strain Promotes Oligodendrocyte Differentiation by Global Changes of Gene Expression |
title_fullStr |
Mechanical Strain Promotes Oligodendrocyte Differentiation by Global Changes of Gene Expression |
title_full_unstemmed |
Mechanical Strain Promotes Oligodendrocyte Differentiation by Global Changes of Gene Expression |
title_sort |
mechanical strain promotes oligodendrocyte differentiation by global changes of gene expression |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cellular Neuroscience |
issn |
1662-5102 |
publishDate |
2017-04-01 |
description |
Differentiation of oligodendrocyte progenitor cells (OPC) to oligodendrocytes and subsequent axon myelination are critical steps in vertebrate central nervous system (CNS) development and regeneration. Growing evidence supports the significance of mechanical factors in oligodendrocyte biology. Here, we explore the effect of mechanical strains within physiological range on OPC proliferation and differentiation, and strain-associated changes in chromatin structure, epigenetics, and gene expression. Sustained tensile strain of 10–15% inhibited OPC proliferation and promoted differentiation into oligodendrocytes. This response to strain required specific interactions of OPCs with extracellular matrix ligands. Applied strain induced changes in nuclear shape, chromatin organization, and resulted in enhanced histone deacetylation, consistent with increased oligodendrocyte differentiation. This response was concurrent with increased mRNA levels of the epigenetic modifier histone deacetylase Hdac11. Inhibition of HDAC proteins eliminated the strain-mediated increase of OPC differentiation, demonstrating a role of HDACs in mechanotransduction of strain to chromatin. RNA sequencing revealed global changes in gene expression associated with strain. Specifically, expression of multiple genes associated with oligodendrocyte differentiation and axon-oligodendrocyte interactions was increased, including cell surface ligands (Ncam, ephrins), cyto- and nucleo-skeleton genes (Fyn, actinins, myosin, nesprin, Sun1), transcription factors (Sox10, Zfp191, Nkx2.2), and myelin genes (Cnp, Plp, Mag). These findings show how mechanical strain can be transmitted to the nucleus to promote oligodendrocyte differentiation, and identify the global landscape of signaling pathways involved in mechanotransduction. These data provide a source of potential new therapeutic avenues to enhance OPC differentiation in vivo. |
topic |
oligodendrocytes oligodendrocyte precursor cell (OPC) oligodendrocyte differentiation mechanical strain multiple sclerosis (MS) mechanotransduction |
url |
http://journal.frontiersin.org/article/10.3389/fncel.2017.00093/full |
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