title: Oct4-induced reprogramming is required for adult brain neural stem cell differentiation into midbrain dopaminergic neurons.
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.
authors.affiliation: Center for Neuroregeneration Research, Harvard Medical School/McLean Hospital, Belmont, Massachusetts, United States of America.
authors.forename: Michela
authors.initials: M
authors.lastname: Deleidi
authors.forename: Oliver
authors.initials: O
authors.lastname: Cooper
authors.forename: Gunnar
authors.initials: G
authors.lastname: Hargus
authors.forename: Adam
authors.initials: A
authors.lastname: Levy
authors.forename: Ole
authors.initials: O
authors.lastname: Isacson
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D065150:Cellular Reprogramming; D004298:Dopamine / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism* / Q000637:transplantation; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism*; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D016133:Polymerase Chain Reaction; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D050814:Octamer Transcription Factor-3; D004298:Dopamine