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dc.contributor.author이상훈-
dc.date.accessioned2016-11-01T08:07:57Z-
dc.date.available2016-11-01T08:07:57Z-
dc.date.issued2015-04-
dc.identifier.citationSTEM CELLS, v. 33, NO 4, Page. 1320-1332en_US
dc.identifier.issn1066-5099-
dc.identifier.issn1549-4918-
dc.identifier.urihttp://onlinelibrary.wiley.com/doi/10.1002/stem.1932/abstract-
dc.identifier.urihttp://hdl.handle.net/20.500.11754/24039-
dc.description.abstractIntracellular Vitamin C (VC) is maintained at high levels in the developing brain by the activity of sodium-dependent VC transporter 2 (Svct2), suggesting specific VC functions in brain development. A role of VC as a cofactor for Fe(II)-2-oxoglutarate-dependent dioxygenases has recently been suggested. We show that VC supplementation in neural stem cell cultures derived from embryonic midbrains greatly enhanced differentiation toward midbrain-type dopamine (mDA) neurons, the neuronal subtype associated with Parkinson's disease. VC induced gain of 5-hydroxymethylcytosine (5hmC) and loss of H3K27m3 in DA phenotype gene promoters, which are catalyzed by Tet1 and Jmjd3, respectively. Consequently, VC enhanced DA phenotype gene transcriptions in the progenitors by Nurr1, a transcription factor critical for mDA neuron development, to be more accessible to the gene promoters. Further mechanism studies including Tet1 and Jmjd3 knockdown/inhibition experiments revealed that both the 5hmC and H3K27m3 changes, specifically in the progenitor cells, are indispensible for the VC-mediated mDA neuron differentiation. We finally show that in Svct2 knockout mouse embryos, mDA neuron formation in the developing midbrain decreased along with the 5hmC/H3k27m3 changes. These findings together indicate an epigenetic role of VC in midbrain DA neuron development. Stem Cells2015;33:1320-1332en_US
dc.description.sponsorshipThis work was supported by grants from the Medical Research Center (2008-0062190) and the Bio & Medical Technology Development Program (2010-0020232), funded by the National Research Foundation of Korea (NRF) of the Ministry of Education, Science and Technology (MEST), Republic of Korea, the research fund of Hanyang University (HY-2014), and NIH Grant AG038739.en_US
dc.language.isoenen_US
dc.publisherWILEY-BLACKWELLen_US
dc.subjectDopamine neuronen_US
dc.subjectFetal midbrainen_US
dc.subjectVitamin Cen_US
dc.subject5hmCen_US
dc.subjectJmjd3en_US
dc.titleVitamin C Facilitates Dopamine Neuron Differentiation in Fetal Midbrain Through TET1-and JMJD3-Dependent Epigenetic Control Manneren_US
dc.typeArticleen_US
dc.relation.no4-
dc.relation.volume33-
dc.identifier.doi10.1002/stem.1932-
dc.relation.page1320-1332-
dc.relation.journalSTEM CELLS-
dc.contributor.googleauthorHe, Xi-Biao-
dc.contributor.googleauthorKim, Mirang-
dc.contributor.googleauthorKim, Seon-Young-
dc.contributor.googleauthorYi, Sang-Hoon-
dc.contributor.googleauthorRhee, Yong-Hee-
dc.contributor.googleauthorKim, Taeho-
dc.contributor.googleauthorLee, Eun-Hye-
dc.contributor.googleauthorPark, Chang-Hwan-
dc.contributor.googleauthorDixit, Shilpy-
dc.contributor.googleauthorHarrison, Fiona E.-
dc.contributor.googleauthorLee, Sang-Hun-
dc.relation.code2015001053-
dc.sector.campusS-
dc.sector.daehakCOLLEGE OF MEDICINE[S]-
dc.sector.departmentDEPARTMENT OF MEDICINE-
dc.identifier.pidleesh-
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COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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