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Oligodendrocyte Intrinsic miR-27a Controls Myelination and Remyelination

64 Pages Posted: 17 Jun 2019 Sneak Peek Status: Published

See all articles by Ajai Tripathi

Ajai Tripathi

Cleveland Clinic - Department of Neurosciences

Christina Volsko

Cleveland Clinic - Department of Neurosciences

Jessie Garcia

University at Buffalo

Eneritz Agirre

Karolinska Institutet

Kevin Allan

Case Western Reserve University

Paul Tesar

Case Western Reserve University - Department of Genetics and Genome Sciences

Bruce Trapp

Cleveland Clinic - Department of Neurosciences

Goncalo Castelo-Branco

Karolinska Institutet

Fraser Sim

University at Buffalo

Ranjan Dutta

Cleveland Clinic - Department of Neurosciences

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Abstract

Remyelination requires the generation of new oligodendrocytes (OLs), which are derived from oligodendrocyte progenitor cells (OPCs). Maturation of OPCs into OLs is a multi-step process and here we describe microRNA, miR-27a, expressed by OLs, as a regulator of OL development and survival. Increased levels of miR-27a was found in OPCs associated with multiple sclerosis (MS) lesions and in animal models of demyelination. Increased levels of miR-27a led to inhibition of OPC proliferation by cell cycle arrest as well as impaired differentiation of human OPCs (hOPCs) and myelination by dysregulating Wnt-β-catenin signaling pathway. In vivo administration of miR-27a led to suppression of myelinogenic signals leading to loss of endogenous myelination and remyelination. Our findings provide evidence supporting a critical role for a steady-state level of OL specific miR-27a in supporting multiple steps in the complex process of OPC maturation and remyelination.

Keywords: Multiple sclerosis, remyelination, miRNA, oligodendrocytes progenitor cells

Suggested Citation

Tripathi, Ajai and Volsko, Christina and Garcia, Jessie and Agirre, Eneritz and Allan, Kevin and Tesar, Paul and Trapp, Bruce and Castelo-Branco, Goncalo and Sim, Fraser and Dutta, Ranjan, Oligodendrocyte Intrinsic miR-27a Controls Myelination and Remyelination (June 17, 2019). CELL-REPORTS-D-19-02332. Available at SSRN: https://ssrn.com/abstract=3405546 or http://dx.doi.org/10.2139/ssrn.3405546
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Ajai Tripathi

Cleveland Clinic - Department of Neurosciences

Cleveland, OH
United States

Christina Volsko

Cleveland Clinic - Department of Neurosciences

Cleveland, OH
United States

Jessie Garcia

University at Buffalo

3435 Main Street
Buffalo, NY 14214
United States

Eneritz Agirre

Karolinska Institutet

Granits väg 4
Solna, 17171
Sweden

Kevin Allan

Case Western Reserve University

10900 Euclid Ave.
Cleveland, OH 44106
United States

Paul Tesar

Case Western Reserve University - Department of Genetics and Genome Sciences

2511 Overlook Road
Cleveland Heights, OH
United States

Bruce Trapp

Cleveland Clinic - Department of Neurosciences ( email )

Cleveland, OH
United States

Goncalo Castelo-Branco

Karolinska Institutet

Granits väg 4
Solna, 17171
Sweden

Fraser Sim

University at Buffalo

3435 Main Street
Buffalo, NY 14214
United States

Ranjan Dutta (Contact Author)

Cleveland Clinic - Department of Neurosciences ( email )

Cleveland, OH
United States

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