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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dc.contributor.author Hargus, Gunnar
dc.contributor.author Deleidi, Michela
dc.contributor.author Cooper, Oliver Jamie
dc.contributor.author Levy, Adam
dc.contributor.author Isacson, Ole Stefan
dc.date.accessioned 2011-12-01T19:15:59Z
dc.date.issued 2011
dc.identifier.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. en_US
dc.identifier.issn 1932-6203 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:5358874
dc.description.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. en_US
dc.language.iso en_US en_US
dc.publisher Public Library of Science en_US
dc.relation.isversionof doi:10.1371/journal.pone.0019926 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3104995/pdf/ en_US
dash.license LAA
dc.subject biology en_US
dc.subject developmental biology en_US
dc.subject stem cells en_US
dc.subject adult stem cells en_US
dc.subject induced pluripotent stem cells en_US
dc.subject neural stem cells en_US
dc.subject neuroscience en_US
dc.subject neurobiology of disease and regeneration en_US
dc.subject medicine en_US
dc.subject neurology en_US
dc.subject Parkinson’s disease en_US
dc.title Oct4-Induced Reprogramming is Required for Adult Brain Neural Stem Cell Differentiation into Midbrain Dopaminergic Neurons en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal PLoS ONE en_US
dash.depositing.author Cooper, Oliver Jamie
dc.date.available 2011-12-01T19:15:59Z
dash.affiliation.other HMS^Psychiatry-McLean Hospital en_US
dash.affiliation.other HMS^Neurology-Massachusetts General Hospital en_US

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