Oct4-Induced Reprogramming is Required for Adult Brain Neural Stem Cell Differentiation into Midbrain Dopaminergic Neurons

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Oct4-Induced Reprogramming is Required for Adult Brain Neural Stem Cell Differentiation into Midbrain Dopaminergic Neurons

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Title: Oct4-Induced Reprogramming is Required for Adult Brain Neural Stem Cell Differentiation into Midbrain Dopaminergic Neurons
Author: Hargus, Gunnar; Deleidi, Michela; Cooper, Oliver Jamie; Levy, Adam; Isacson, Ole Stefan

Note: Order does not necessarily reflect citation order of authors.

Citation: Deleidi, Michela, Oliver Cooper, Gunnar Hargus, Adam Levy, and Ole Isacson. 2011. Oct4-induced reprogramming is required for adult brain neural stem cell differentiation into midbrain dopaminergic neurons. PLoS ONE 6(5): e19926.
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Abstract: Neural stem cells (NSCs) lose their competency to generate region-specific neuronal populations at an early stage during embryonic brain development. Here we investigated whether epigenetic modifications can reverse the regional restriction of mouse adult brain subventricular zone (SVZ) NSCs. Using a variety of chemicals that interfere with DNA methylation and histone acetylation, we showed that such epigenetic modifications increased neuronal differentiation but did not enable specific regional patterning, such as midbrain dopaminergic (DA) neuron generation. Only after Oct-4 overexpression did adult NSCs acquire a pluripotent state that allowed differentiation into midbrain DA neurons. DA neurons derived from Oct4-reprogrammed NSCs improved behavioural motor deficits in a rat model of Parkinson's disease (PD) upon intrastriatal transplantation. Here we report for the first time the successful differentiation of SVZ adult NSCs into functional region-specific midbrain DA neurons, by means of Oct-4 induced pluripotency.
Published Version: doi:10.1371/journal.pone.0019926
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3104995/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:5358874

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