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dc.contributor.authorBellmaine, SF
dc.contributor.authorOvchinnikov, DA
dc.contributor.authorManallack, DT
dc.contributor.authorCuddy, CE
dc.contributor.authorElefanty, AG
dc.contributor.authorStanley, EG
dc.contributor.authorWolvetang, EJ
dc.contributor.authorWilliams, SJ
dc.contributor.authorPera, M
dc.date.accessioned2020-12-21T02:15:43Z
dc.date.available2020-12-21T02:15:43Z
dc.date.issued2017-09-08
dc.identifierpii: 24502
dc.identifier.citationBellmaine, S. F., Ovchinnikov, D. A., Manallack, D. T., Cuddy, C. E., Elefanty, A. G., Stanley, E. G., Wolvetang, E. J., Williams, S. J. & Pera, M. (2017). Inhibition of DYRK1A disrupts neural lineage specificationin human pluripotent stem cells. ELIFE, 6, https://doi.org/10.7554/eLife.24502.
dc.identifier.issn2050-084X
dc.identifier.urihttp://hdl.handle.net/11343/256850
dc.description.abstractGenetic analysis has revealed that the dual specificity protein kinase DYRK1A has multiple roles in the development of the central nervous system. Increased DYRK1A gene dosage, such as occurs in Down syndrome, is known to affect neural progenitor cell differentiation, while haploinsufficiency of DYRK1A is associated with severe microcephaly. Using a set of known and newly synthesized DYRK1A inhibitors, along with CRISPR-mediated gene activation and shRNA knockdown of DYRK1A, we show here that chemical inhibition or genetic knockdown of DYRK1A interferes with neural specification of human pluripotent stem cells, a process equating to the earliest stage of human brain development. Specifically, DYRK1A inhibition insulates the self-renewing subpopulation of human pluripotent stem cells from powerful signals that drive neural induction. Our results suggest a novel mechanism for the disruptive effects of the absence or haploinsufficiency of DYRK1A on early mammalian development, and reveal a requirement for DYRK1A in the acquisition of competence for differentiation in human pluripotent stem cells.
dc.languageEnglish
dc.publisherELIFE SCIENCES PUBLICATIONS LTD
dc.titleInhibition of DYRK1A disrupts neural lineage specificationin human pluripotent stem cells
dc.typeJournal Article
dc.identifier.doi10.7554/eLife.24502
melbourne.affiliation.departmentAnatomy and Neuroscience
melbourne.affiliation.departmentSchool of Chemistry
melbourne.affiliation.departmentPaediatrics (RCH)
melbourne.source.titleeLife
melbourne.source.volume6
dc.rights.licenseCC BY
melbourne.elementsid1234201
melbourne.contributor.authorPera, Martin
melbourne.contributor.authorStanley, Edouard
melbourne.contributor.authorElefanty, Andrew
melbourne.contributor.authorWilliams, Spencer
melbourne.contributor.authorBellmaine, Stephanie
melbourne.contributor.authorCuddy, Claire
dc.identifier.eissn2050-084X
melbourne.accessrightsOpen Access


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