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dc.contributor.authorVarga, Balazs
dc.contributor.authorFaiz, Maryam
dc.contributor.authorPivonkova, Helena
dc.contributor.authorKhelifi, Gabriel
dc.contributor.authorYang, Huijuan
dc.contributor.authorGao, Shangbang
dc.contributor.authorLinderoth, Emma
dc.contributor.authorZhen, Mei
dc.contributor.authorKaradottir, Thora
dc.contributor.authorHussein, Samer M
dc.contributor.authorNagy, Andras
dc.date.accessioned2022-05-23T15:01:28Z
dc.date.available2022-05-23T15:01:28Z
dc.date.issued2022-05-23
dc.date.submitted2019-11-28
dc.identifier.issn2041-1723
dc.identifier.others41467-022-29839-8
dc.identifier.other29839
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/337405
dc.description.abstractThe cerebral cortex develops from dorsal forebrain neuroepithelial progenitor cells. Following the initial expansion of the progenitor cell pool, these cells generate neurons of all the cortical layers and then astrocytes and oligodendrocytes. Yet, the regulatory pathways that control the expansion and maintenance of the progenitor cell pool are currently unknown. Here we define six basic pathway components that regulate proliferation of cortically specified human neuroepithelial stem cells (cNESCs) in vitro without the loss of cerebral cortex developmental potential. We show that activation of FGF and inhibition of BMP and ACTIVIN A signalling are required for long-term cNESC proliferation. We also demonstrate that cNESCs preserve dorsal telencephalon-specific potential when GSK3, AKT and nuclear CATENIN-β1 activity are low. Remarkably, regulation of these six pathway components supports the clonal expansion of cNESCs. Moreover, cNESCs differentiate into lower- and upper-layer cortical neurons in vitro and in vivo. The identification of mechanisms that drive the neuroepithelial stem cell self-renewal and differentiation and preserve this potential in vitro is key to developing regenerative and cell-based therapeutic approaches to treat neurological conditions.
dc.languageen
dc.publisherSpringer Science and Business Media LLC
dc.subjectArticle
dc.subject/631/378/2183/2182
dc.subject/631/532/2182
dc.subject/631/532/2441
dc.subject/631/61/2320
dc.subject/631/136/2441
dc.subject/13/106
dc.subject/38/61
dc.subject/38/77
dc.subject/38/91
dc.subject/13/100
dc.subject/14/63
dc.subject/14/19
dc.subjectarticle
dc.titleSignal requirement for cortical potential of transplantable human neuroepithelial stem cells.
dc.typeArticle
dc.date.updated2022-05-23T15:01:27Z
prism.issueIdentifier1
prism.publicationNameNat Commun
prism.volume13
dc.identifier.doi10.17863/CAM.84817
dcterms.dateAccepted2022-03-21
rioxxterms.versionofrecord10.1038/s41467-022-29839-8
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidVarga, Balazs [0000-0002-4005-1203]
dc.contributor.orcidPivonkova, Helena [0000-0003-2790-9778]
dc.contributor.orcidKhelifi, Gabriel [0000-0002-8973-7345]
dc.contributor.orcidGao, Shangbang [0000-0001-5431-4628]
dc.contributor.orcidZhen, Mei [0000-0003-0086-9622]
dc.contributor.orcidKaradottir, Thora [0000-0001-9675-2722]
dc.contributor.orcidNagy, Andras [0000-0003-4311-0413]
dc.identifier.eissn2041-1723
cam.issuedOnline2022-05-23


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