Yujin Kim


Identifying the Fate Determining Step of the Differentiation of Oligodendrocyte Progenitor Cells from Mouse Induced Pluripotent Stem Cells

Cell-based therapy utilizing oligodendrocyte progenitor cells (OPCs) is a promising therapeutic strategy for numerous neurodegenerative disorders that involve the loss of myelin sheaths in the central nervous system (CNS). OPCs derived from induced pluripotent stem cells (iPSCs) can restore myelin specifically in demyelinated/dysmyelinated regions. In order to establish a more efficient protocol for generating OPCs from human-induced pluripotent stem cells (hiPSCs), this study focused on better understanding the fate determining step in the directed differentiation of OPCs from iPSCs. Pre-established protocols for the generation of motoneurons (MNs) and OPCs from mouse-induced pluripotent stem cells (miPSCs) were manipulated. miPSCs derived from the strain JBL6 3F2 were used to proceed through two switch protocols where the original protocols for MNs and OPCs were crossed over at the specification stage, post induction. The two original protocols served as controls. Immunohistochemistry (IHC) was performed for immunofluorescence (IF) staining of DAPI, BIII-tubulin, and Olig2 to visualize the nuclei, MNs, and OPCs, respectively. Both switch groups resulted in significant amounts of MNs and OPCs. The miPSC group subjected to initial MN induction presented similar numbers of MNs and OPCs while the group that was introduced with initial OPC induction produced a significantly higher number of MNs (p < 0.01).This indicated that the fate determination of OPC occured in the specification or expansion stage of OPC induction, suggesting the crucial effects of either retinoic acid (RA) concentration in the specification media or the expansion media on OPC differentiation, both of which may serve as the focus of further research to improve the duration and yield of OPC differentiation from hiPSCs.

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