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Original Article |
1 Department of Medical Physiology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands
2 Department of Cell Biology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands
* To whom correspondence should be addressed. E-mail: j.c.v.m.copray{at}med.umcg.nl.
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Abstract |
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Differentiation induction of neural stem cells (NSCs) into oligodendrocytes during embryogenesis is the result of a complex interaction between local induction factors and intracellular transcription factors. At the early stage of differentiation, in particular the helix-loop-helix transcription factors Olig1 and Olig2 have been shown essential for oligodendrocyte lineage determination. In view of the possible application of NSCs as a source for remyelinating cell transplants in demyelinating diseases (e.g. MS), in-vitro procedures have to be developed to drive the oligodendrocyte differentiation process. Mere culture in medium supplemented with major embryonic oligodendrogenic induction factors, such as sonic hedgehog (Shh), results in oligodendrocyte differentiation of only about 10% of NSCs. Previously we have shown that induction of Olig1 expression by gene transfection could indeed initiate the first stage of oligodendrocyte differentiation in NSCs but appeared to be unable to generate fully maturated, functional oligodendrocytes. In this study we have transfected NSCs, isolated from embryonic mouse brain, with the Olig2 gene and found that the introduced overexpression of Olig2 could induce the development of fully maturated oligodendrocytes, expressing the transcription factor Nkx2.2 and all major myelin specific proteins. Moreover, Olig2-transfected NSCs, in contrast to nontransfected NSCs, developed into actively remyelinating oligodendrocytes after transplantation in the corpus callosum of long-term cuprizone-fed mice, an animal model for demyelination. Our results show that transfection of genes encoding for oligodendrogenic transcription factors can be an efficient way to induce the differentiation of NSCs into functional oligodendrocytes.
Key Words. Neural stem cells, oligendrocyte progenitor cells, embryonic, Olig, Nkx2.2
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