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dc.contributor.authorArber, Charles
dc.contributor.authorPrecious, Sophie
dc.contributor.authorCambray, Serafi
dc.contributor.authorRisner-Janiczek, Jessica
dc.contributor.authorKelly, Claire
dc.contributor.authorNoakes, Zoe
dc.contributor.authorFjodorova, Marija
dc.contributor.authorHeuer, Andreas
dc.contributor.authorUngless, Mark
dc.contributor.authorRodriguez, Tristan
dc.contributor.authorRosser, Anne
dc.contributor.authorDunnett, Stephen
dc.contributor.authorLi, Meng
dc.date.accessioned2016-07-26T14:54:10Z
dc.date.available2016-07-26T14:54:10Z
dc.date.issued2015-04-01
dc.identifier.citationAber, C., Precious, S. V., Cambray, S., Risner-Janiczek, J.R., Kelly, C., Noakes, Z., Fjodorova, M., Heuer, A., Ungless, M.A., Rodriguez, T.A., Rosser, A.E., Dunnett, S.B. and Li, M. (2015) 'Activin A directs striatal projection neuron differentiation of human pluripotent stem cells', Development, 142 (7), pp.1375-1386.en_US
dc.identifier.issn1477-9129
dc.identifier.urihttp://hdl.handle.net/10369/7986
dc.descriptionThis article was published in Development on 1st April 2015 (online), available at http://dev.biologists.org/content/142/7/1375en_US
dc.description.abstractThe efficient generation of striatal neurons from human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) is fundamental for realising their promise in disease modelling, pharmaceutical drug screening and cell therapy for Huntington's disease. GABAergic medium-sized spiny neurons (MSNs) are the principal projection neurons of the striatum and specifically degenerate in the early phase of Huntington's disease. Here we report that activin A induces lateral ganglionic eminence (LGE) characteristics in nascent neural progenitors derived from hESCs and hiPSCs in a sonic hedgehog-independent manner. Correct specification of striatal phenotype was further demonstrated by the induction of the striatal transcription factors CTIP2, GSX2 and FOXP2. Crucially, these human LGE progenitors readily differentiate into postmitotic neurons expressing the striatal projection neuron signature marker DARPP32, both in culture and following transplantation in the adult striatum in a rat model of Huntington's disease. Activin-induced neurons also exhibit appropriate striatal-like electrophysiology in vitro. Together, our findings demonstrate a novel route for efficient differentiation of GABAergic striatal MSNs from human pluripotent stem cellsen_US
dc.publisherThe Company of Biologistsen_US
dc.relation.ispartofseriesDevelopment;
dc.rightsCreative Commons (CC-BY 3.0) license
dc.rights.urihttps://creativecommons.org/licenses/by/3.0/
dc.subjectneuronsen_US
dc.subjectstem cellsen_US
dc.subjectdisease modellingen_US
dc.subjectdrug screeningen_US
dc.subjecttransplantationen_US
dc.titleActivin A directs striatal projection neuron differentiation of human pluripotent stem cellsen_US
dc.typeArticleen_US
dc.identifier.doihttp://dx.doi.org/10.1242/dev.117093
dc.date.dateAccepted2015-02-06


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