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Generation of Dopamine Neurons from Rodent Fibroblasts through the Expandable Neural Precursor Cell Stage.

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dc.contributor.authorLim, MS-
dc.contributor.authorChang, MY-
dc.contributor.authorKim, SM-
dc.contributor.authorYi, SH-
dc.contributor.authorSuh-Kim, H-
dc.contributor.authorJung, SJ-
dc.contributor.authorKim, MJ-
dc.contributor.authorKim, JH-
dc.contributor.authorLee, YS-
dc.contributor.authorLee, SY-
dc.contributor.authorKim, DW-
dc.contributor.authorLee, SH-
dc.contributor.authorPark, CH-
dc.date.accessioned2017-06-13T06:54:08Z-
dc.date.available2017-06-13T06:54:08Z-
dc.date.issued2015-
dc.identifier.issn0021-9258-
dc.identifier.urihttp://repository.ajou.ac.kr/handle/201003/14148-
dc.description.abstractRecent groundbreaking work has demonstrated that combined expression of the transcription factors Brn2, Ascl1, and Myt1L (BAM; also known as Wernig factors) convert mouse fibroblasts into postmitotic neuronal cells. However, questions remain regarding whether trans-conversion is achieved directly or involves an intermediary precursor stage. Trans-conversion toward expandable neural precursor cells (NPCs) is more useful than direct one-step neuron formation with respect to yielding a sufficient number of cells and the feasibility of manipulating NPC differentiation toward certain neuron subtypes. Here, we show that co-expression of Wernig factors and Bcl-xL induces fibroblast conversion into NPCs (induced NPCs (iNPCs)) that are highly expandable for >100 passages. Gene expression analyses showed that the iNPCs exhibited high expression of common NPC genes but not genes specific to defined embryonic brain regions. This finding indicated that a regional identity of iNPCs was not established. Upon induction, iNPCs predominantly differentiated into astrocytes. However, the differentiation potential was not fixed and could be efficiently manipulated into general or specific subtypes of neurons by expression of additional genes. Specifically, overexpression of Nurr1 and Foxa2, transcription factors specific for midbrain dopamine neuron development, drove iNPCs to yield mature midbrain dopamine neurons equipped with presynaptic DA neuronal functions. We further assessed the therapeutic potential of iNPCs in Parkinson disease model rats.-
dc.language.isoen-
dc.subject.MESHAnimals-
dc.subject.MESHBasic Helix-Loop-Helix Transcription Factors-
dc.subject.MESHCell Transdifferentiation-
dc.subject.MESHCellular Reprogramming-
dc.subject.MESHDopamine-
dc.subject.MESHDopaminergic Neurons-
dc.subject.MESHFibroblasts-
dc.subject.MESHGene Expression-
dc.subject.MESHHepatocyte Nuclear Factor 3-beta-
dc.subject.MESHMesencephalon-
dc.subject.MESHMice-
dc.subject.MESHMice, Inbred C57BL-
dc.subject.MESHMice, Inbred ICR-
dc.subject.MESHMice, Transgenic-
dc.subject.MESHNerve Tissue Proteins-
dc.subject.MESHNeural Stem Cells-
dc.subject.MESHNuclear Receptor Subfamily 4, Group A, Member 2-
dc.subject.MESHPOU Domain Factors-
dc.subject.MESHParkinsonian Disorders-
dc.subject.MESHRats-
dc.subject.MESHRats, Inbred Lew-
dc.subject.MESHRats, Wistar-
dc.subject.MESHTranscription Factors-
dc.titleGeneration of Dopamine Neurons from Rodent Fibroblasts through the Expandable Neural Precursor Cell Stage.-
dc.typeArticle-
dc.identifier.pmid26023233-
dc.identifier.urlhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4498077/-
dc.contributor.affiliatedAuthor서, 해영-
dc.type.localJournal Papers-
dc.identifier.doi10.1074/jbc.M114.629808-
dc.citation.titleThe Journal of biological chemistry-
dc.citation.volume290-
dc.citation.number28-
dc.citation.date2015-
dc.citation.startPage17401-
dc.citation.endPage17414-
dc.identifier.bibliographicCitationThe Journal of biological chemistry, 290(28). : 17401-17414, 2015-
dc.identifier.eissn1083-351X-
dc.relation.journalidJ000219258-
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Anatomy
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