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dc.contributor.authorAnderson, DJ
dc.contributor.authorKaplan, DI
dc.contributor.authorBell, KM
dc.contributor.authorKoutsis, K
dc.contributor.authorHaynes, JM
dc.contributor.authorMills, RJ
dc.contributor.authorPhelan, DG
dc.contributor.authorQian, EL
dc.contributor.authorLeitoguinho, AR
dc.contributor.authorArasaratnam, D
dc.contributor.authorLabonne, T
dc.contributor.authorNg, ES
dc.contributor.authorDavis, RP
dc.contributor.authorCasini, S
dc.contributor.authorPassier, R
dc.contributor.authorHudson, JE
dc.contributor.authorPorrello, ER
dc.contributor.authorCosta, MW
dc.contributor.authorRafii, A
dc.contributor.authorCurl, CL
dc.contributor.authorDelbridge, LM
dc.contributor.authorHarvey, RP
dc.contributor.authorOshlack, A
dc.contributor.authorCheung, MM
dc.contributor.authorMummery, CL
dc.contributor.authorPetrou, S
dc.contributor.authorElefanty, AG
dc.contributor.authorStanley, EG
dc.contributor.authorElliott, DA
dc.date.accessioned2020-12-17T03:15:14Z
dc.date.available2020-12-17T03:15:14Z
dc.date.issued2018-04-10
dc.identifierpii: 10.1038/s41467-018-03714-x
dc.identifier.citationAnderson, D. J., Kaplan, D. I., Bell, K. M., Koutsis, K., Haynes, J. M., Mills, R. J., Phelan, D. G., Qian, E. L., Leitoguinho, A. R., Arasaratnam, D., Labonne, T., Ng, E. S., Davis, R. P., Casini, S., Passier, R., Hudson, J. E., Porrello, E. R., Costa, M. W., Rafii, A. ,... Elliott, D. A. (2018). NKX2-5 regulates human cardiomyogenesis via a HEY2 dependent transcriptional network. NATURE COMMUNICATIONS, 9 (1), https://doi.org/10.1038/s41467-018-03714-x.
dc.identifier.issn2041-1723
dc.identifier.urihttp://hdl.handle.net/11343/254807
dc.description.abstractCongenital heart defects can be caused by mutations in genes that guide cardiac lineage formation. Here, we show deletion of NKX2-5, a critical component of the cardiac gene regulatory network, in human embryonic stem cells (hESCs), results in impaired cardiomyogenesis, failure to activate VCAM1 and to downregulate the progenitor marker PDGFRα. Furthermore, NKX2-5 null cardiomyocytes have abnormal physiology, with asynchronous contractions and altered action potentials. Molecular profiling and genetic rescue experiments demonstrate that the bHLH protein HEY2 is a key mediator of NKX2-5 function during human cardiomyogenesis. These findings identify HEY2 as a novel component of the NKX2-5 cardiac transcriptional network, providing tangible evidence that hESC models can decipher the complex pathways that regulate early stage human heart development. These data provide a human context for the evaluation of pathogenic mutations in congenital heart disease.
dc.languageEnglish
dc.publisherNATURE PUBLISHING GROUP
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleNKX2-5 regulates human cardiomyogenesis via a HEY2 dependent transcriptional network
dc.typeJournal Article
dc.identifier.doi10.1038/s41467-018-03714-x
melbourne.affiliation.departmentFlorey Department of Neuroscience and Mental Health
melbourne.affiliation.departmentPaediatrics (RCH)
melbourne.affiliation.departmentPhysiology
melbourne.affiliation.departmentSchool of Physics
melbourne.source.titleNature Communications
melbourne.source.volume9
melbourne.source.issue1
dc.rights.licenseCC BY
melbourne.elementsid1323067
melbourne.contributor.authorCheung, Michael
melbourne.contributor.authorPorrello, Enzo
melbourne.contributor.authorCurl, Claire
melbourne.contributor.authorOshlack, Alicia
melbourne.contributor.authorPetrou, Steven
melbourne.contributor.authorElliott, David
melbourne.contributor.authorKaplan, David
melbourne.contributor.authorDelbridge, Leanne
melbourne.contributor.authorElefanty, Andrew
melbourne.contributor.authorStanley, Edouard
dc.identifier.eissn2041-1723
melbourne.accessrightsOpen Access


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