Linked Life Data

18669911

Source:http://linkedlifedata.com/resource/pubmed/id/18669911

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2008-10-21
pubmed:abstractText
In the retina, as elsewhere in the central nervous system, neurogenesis precedes gliogenesis; that is, the only glia in the retina, Müller cells, are born when the majority of neurons have already been generated. However, our understanding of how the multipotent retinal stem cells/progenitors choose to differentiate along neuronal and glial lineages is unclear. This information is important in promoting directed differentiation of retinal stem cells/progenitors in an ex vivo or in vivo stem cell approach to treating degenerative retinal diseases. Here, using the neurosphere assay, we demonstrate that ciliary neurotrophic factor (CNTF), acting in a concentration-dependent manner, influences the simultaneous differentiation of retinal stem cells/progenitors into neurons or glia. At low CNTF concentrations differentiation of bipolar cells is promoted, whereas high CNTF concentrations facilitate Müller cell differentiation. The two concentrations of CNTF lead to differential activation of mitogen-activated protein kinase and Janus kinase-signal transducer and activator of transcription (Jak-STAT) pathways, with recruitment of the former and the latter for the differentiation of bipolar and Müller cells, respectively. The concentration-dependent recruitment of two disparate pathways toward neurogenesis and gliogenesis occurs in concert with Notch signaling. Furthermore, we demonstrate that the attenuation of Jak-STAT signaling along with Notch signaling facilitates the differentiation of retinal stem cells/progenitors along the rod photoreceptor lineage in vivo. Our observations posit CNTF-mediated signaling as a molecular switch for neuronal versus glial differentiation of retinal stem cells/progenitors and a molecular target for directed neuronal differentiation of retinal stem cells/progenitors as an approach to addressing degenerative changes in the retina. Disclosure of potential conflicts of interest is found at the end of this article.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1549-4918
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
26
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2611-24
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:18669911-Animals, pubmed-meshheading:18669911-Cell Differentiation, pubmed-meshheading:18669911-Ciliary Neurotrophic Factor, pubmed-meshheading:18669911-Dose-Response Relationship, Drug, pubmed-meshheading:18669911-Glial Fibrillary Acidic Protein, pubmed-meshheading:18669911-Humans, pubmed-meshheading:18669911-Janus Kinases, pubmed-meshheading:18669911-Mitogen-Activated Protein Kinases, pubmed-meshheading:18669911-Neuroglia, pubmed-meshheading:18669911-Neurons, pubmed-meshheading:18669911-Promoter Regions, Genetic, pubmed-meshheading:18669911-Rats, pubmed-meshheading:18669911-Receptors, Notch, pubmed-meshheading:18669911-Retina, pubmed-meshheading:18669911-STAT Transcription Factors, pubmed-meshheading:18669911-Signal Transduction, pubmed-meshheading:18669911-Stem Cells
pubmed:year
2008
pubmed:articleTitle
Ciliary neurotrophic factor-mediated signaling regulates neuronal versus glial differentiation of retinal stem cells/progenitors by concentration-dependent recruitment of mitogen-activated protein kinase and Janus kinase-signal transducer and activator of transcription pathways in conjunction with Notch signaling.
pubmed:affiliation
Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, Nebraska, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't