J Chem Neuroanat. 2018 Mar 9. pii: S0891-0618(17)30209-0. doi: 10.1016/j.jchemneu.2018.03.001. [Epub ahead of print]

Overexpression of miR-219 Promotes Differentiation of Human Induced Pluripotent Stem Cells into pre-Oligodendrocyte.

Nazari B¹, Soleimani M², Ebrahimi Barough S³, Enderami SE⁴, Kazemi M³, Negahdari B¹, Sadroddiny E⁵, Ai J⁶.

Abstract

Oligodendrocytes play critical roles in the central nervous system (CNS) thorough producing myelin sheaths around axons. There are a variety of approaches to produce oligodendrocytes in vitro and in vivo which are a subject of interest in many studies. A new approach to induce this differentiation is using microRNA 219 (miR-219). However, this new approach suffers from a lack of studies regarding the effect of miR-219 on differentiating human induced pluripotent stem cells (hiPSCs) to oligodendrocytes. This study aimed to assess the impact of miR-219-overexpression on hiPSCs. Initially, hiPSCs were induced with basic fibroblast growth factor (bFGF), epidermalgrowth factor (EGF) and platelet-derived growth factor (PDGF)-AA, then, miR-219- green fluorescent protein (GFP)-expressing lentiviruses were utilized for cell infection. Microscopic observation revealed significant morphological changes and data obtained from quantitative reverse transcription PCR and immunofluorescence analysis of differentiated cells showed that the expression of various oligodendrocyte stage-specific markers such as Nestin, Olig2, Sox10, PDGFRα, A2B5, O4, and MBP increased. In addition, higher expressions of pre-oligodendrocyte markers were detected in the cells transduced with miR-219 lentivirus in comparison with the cells treated with triiodothyronine (T3). These results suggest that overexpression of miR-219 promotes differentiation of hiPSCs to pre-oligodendrocyte cells, providing a potential source for cell therapy by replacing and restoring the lost cell function in neurodegenerative and demyelinating diseases.