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dc.contributor.advisorDan Hoeppner, MD (Johns Hopkins Medical School, Lieber Institute for Brain Development)
dc.contributor.authorAdepoju, Adedamola
dc.contributor.authorMicali, Nicola
dc.contributor.authorOgawa, Kazuya
dc.contributor.authorHoeppner, Daniel J.
dc.contributor.authorMcKay, Ronald D.G.
dc.date2022-08-11T08:10:55.000
dc.date.accessioned2022-08-23T17:24:45Z
dc.date.available2022-08-23T17:24:45Z
dc.date.issued2014-03-01
dc.date.submitted2015-10-07
dc.identifier.citationStem Cells. 2014 Mar;32(3):770-8. doi: 10.1002/stem.1575. <a href="http://dx.doi.org/10.1002/stem.1575">Link to article on publisher's site</a>
dc.identifier.issn1066-5099 (Linking)
dc.identifier.doi10.1002/stem.1575
dc.identifier.pmid24155149
dc.identifier.urihttp://hdl.handle.net/20.500.14038/49258
dc.description<p>Medical student Adedamola Adepoju participated in this study as part of the Senior Scholars research program at the University of Massachusetts Medical School.</p>
dc.description.abstractThe ex vivo expansion of stem cells is making major contribution to biomedical research. The multipotent nature of neural precursors acutely isolated from the developing central nervous system has been established in a series of studies. Understanding the mechanisms regulating cell expansion in tissue culture would support their expanded use either in cell therapies or to define disease mechanisms. Basic fibroblast growth factor (FGF2) and insulin, ligands for tyrosine kinase receptors, are sufficient to sustain neural stem cells (NSCs) in culture. Interestingly, real-time imaging shows that these cells become multipotent every time they are passaged. Here, we analyze the role of FGF2 and insulin in the brief period when multipotent cells are present. FGF2 signaling results in the phosphorylation of Erk1/2, and activation of c-Fos and c-Jun that lead to elevated cyclin D mRNA levels. Insulin signals through the PI3k/Akt pathway to regulate cyclins at the post-transcriptional level. This precise Boolean regulation extends our understanding of the proliferation of multipotent NSCs and provides a basis for further analysis of proliferation control in the cell states defined by real-time mapping of the cell lineages that form the central nervous system.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=24155149&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1002/stem.1575
dc.subjectAnimals
dc.subjectCell Proliferation
dc.subjectCyclin D
dc.subjectDNA
dc.subjectFemale
dc.subjectFibroblast Growth Factor 2
dc.subjectInsulin
dc.subjectIntracellular Space
dc.subjectMice
dc.subjectMice, Inbred C57BL
dc.subjectModels, Biological
dc.subjectMultipotent Stem Cells
dc.subjectNeural Stem Cells
dc.subjectProtein Biosynthesis
dc.subjectProto-Oncogene Proteins c-fos
dc.subjectProto-Oncogene Proteins c-jun
dc.subjectSignal Transduction
dc.subjectTranscription, Genetic
dc.subjectCell Biology
dc.subjectDevelopmental Biology
dc.subjectDevelopmental Neuroscience
dc.subjectMolecular and Cellular Neuroscience
dc.titleFGF2 and insulin signaling converge to regulate cyclin D expression in multipotent neural stem cells
dc.typeJournal Article
dc.source.journaltitleStem cells (Dayton, Ohio)
dc.source.volume32
dc.source.issue3
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/ssp/202
dc.identifier.contextkey7688603
html.description.abstract<p>The ex vivo expansion of stem cells is making major contribution to biomedical research. The multipotent nature of neural precursors acutely isolated from the developing central nervous system has been established in a series of studies. Understanding the mechanisms regulating cell expansion in tissue culture would support their expanded use either in cell therapies or to define disease mechanisms. Basic fibroblast growth factor (FGF2) and insulin, ligands for tyrosine kinase receptors, are sufficient to sustain neural stem cells (NSCs) in culture. Interestingly, real-time imaging shows that these cells become multipotent every time they are passaged. Here, we analyze the role of FGF2 and insulin in the brief period when multipotent cells are present. FGF2 signaling results in the phosphorylation of Erk1/2, and activation of c-Fos and c-Jun that lead to elevated cyclin D mRNA levels. Insulin signals through the PI3k/Akt pathway to regulate cyclins at the post-transcriptional level. This precise Boolean regulation extends our understanding of the proliferation of multipotent NSCs and provides a basis for further analysis of proliferation control in the cell states defined by real-time mapping of the cell lineages that form the central nervous system.</p>
dc.identifier.submissionpathssp/202
dc.contributor.departmentSchool of Medicine
dc.source.pages770-8


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