Linked Life Data

20049900

Source:http://linkedlifedata.com/resource/pubmed/id/20049900

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2010-3-31
pubmed:abstractText
Effective dopamine (DA) neuron differentiation from neural precursor cells (NPCs) is prerequisite for precursor/stem cell-based therapy of Parkinson's disease (PD). Nurr1, an orphan nuclear receptor, has been reported as a transcription factor that can drive DA neuron differentiation from non-dopaminergic NPCs in vitro. However, Nurr1 alone neither induces full neuronal maturation nor expression of proteins found specifically in midbrain DA neurons. In addition, Nurr1 expression is inefficient in inducing DA phenotype expression in NPCs derived from certain species such as mouse and human. We show here that Foxa2, a forkhead transcription factor whose role in midbrain DA neuron development was recently revealed, synergistically cooperates with Nurr1 to induce DA phenotype acquisition, midbrain-specific gene expression, and neuronal maturation. Thus, the combinatorial expression of Nurr1 and Foxa2 in NPCs efficiently yielded fully differentiated nigral (A9)-type midbrain neurons with clearly detectable DA neuronal activities. The effects of Foxa2 in DA neuron generation were observed regardless of the brain regions or species from which NPCs were derived. Furthermore, DA neurons generated by ectopic Foxa2 expression were more resistant to toxins. Importantly, Foxa2 expression resulted in a rapid cell cycle exit and reduced cell proliferation. Consistently, transplantation of NPCs transduced with Nurr1 and Foxa2 generated grafts enriched with midbrain-type DA neurons but reduced number of proliferating cells, and significantly reversed motor deficits in a rat PD model. Our findings can be applied to ongoing attempts to develop an efficient and safe precursor/stem cell-based therapy for PD.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1549-4918
pubmed:author
pubmed:issnType
Electronic
pubmed:day
31
pubmed:volume
28
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
501-12
pubmed:meshHeading
pubmed-meshheading:20049900-Animals, pubmed-meshheading:20049900-Cell Differentiation, pubmed-meshheading:20049900-Cell Proliferation, pubmed-meshheading:20049900-Cell Survival, pubmed-meshheading:20049900-Cells, Cultured, pubmed-meshheading:20049900-Dopamine, pubmed-meshheading:20049900-Hepatocyte Nuclear Factor 3-beta, pubmed-meshheading:20049900-Humans, pubmed-meshheading:20049900-Mice, pubmed-meshheading:20049900-Neurogenesis, pubmed-meshheading:20049900-Neurons, pubmed-meshheading:20049900-Nuclear Receptor Subfamily 4, Group A, Member 2, pubmed-meshheading:20049900-Parkinson Disease, pubmed-meshheading:20049900-Phenotype, pubmed-meshheading:20049900-Rats, pubmed-meshheading:20049900-Rats, Sprague-Dawley, pubmed-meshheading:20049900-Stem Cell Transplantation, pubmed-meshheading:20049900-Stem Cells, pubmed-meshheading:20049900-Substantia Nigra, pubmed-meshheading:20049900-Tissue Therapy, pubmed-meshheading:20049900-Transfection, pubmed-meshheading:20049900-Treatment Outcome
pubmed:year
2010
pubmed:articleTitle
Foxa2 and Nurr1 synergistically yield A9 nigral dopamine neurons exhibiting improved differentiation, function, and cell survival.
pubmed:affiliation
Department of Biochemistry and Molecular Biology, Hanyang University, Seoul, Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't