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An orthologous epigenetic gene expression signature derived from differentiating embryonic stem cells identifies regulators of cardiogenesis
Busser B.W.1; Lin Y.1; Yang Y.1; Zhu J.1; Chen G.1; Michelson A.M.1
2015-10-20
Source PublicationPLoS ONE
ISSN19326203
Volume10Issue:10
Abstract

Here we used predictive gene expression signatures within a multi-species framework to identify the genes that underlie cardiac cell fate decisions in differentiating embryonic stem cells. We show that the overlapping orthologous mouse and human genes are the most accurate candidate cardiogenic genes as these genes identified the most conserved developmental pathways that characterize the cardiac lineage. An RNAi-based screen of the candidate genes in Drosophila uncovered numerous novel cardiogenic genes. shRNA knockdown combined with transcriptome profiling of the newly-identified transcription factors zinc finger protein 503 and zinc finger E-box binding homeobox 2 and the well-known cardiac regulatory factor NK2 homeobox 5 revealed that zinc finger E-box binding homeobox 2 activates terminal differentiation genes required for cardiomyocyte structure and function whereas zinc finger protein 503 and NK2 homeobox 5 are required for specification of the cardiac lineage.We further demonstrated that an essential role of NK2 homeobox 5 and zinc finger protein 503 in specification of the cardiac lineage is the repression of gene expression programs characteristic of alternative cell fates. Collectively, these results show that orthologous gene expression signatures can be used to identify conserved cardiogenic pathways. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

DOI10.1371/journal.pone.0141066
URLView the original
Indexed BySCI
Language英语
WOS Research AreaScience & Technology - Other Topics
WOS SubjectMultidisciplinary Sciences
WOS IDWOS:000363028100110
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Cited Times [WOS]:3   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Affiliation1.National Heart, Lung, and Blood Institute
2.Cellectis Inc
3.Universidade de Macau
Recommended Citation
GB/T 7714
Busser B.W.,Lin Y.,Yang Y.,et al. An orthologous epigenetic gene expression signature derived from differentiating embryonic stem cells identifies regulators of cardiogenesis[J]. PLoS ONE,2015,10(10).
APA Busser B.W.,Lin Y.,Yang Y.,Zhu J.,Chen G.,&Michelson A.M..(2015).An orthologous epigenetic gene expression signature derived from differentiating embryonic stem cells identifies regulators of cardiogenesis.PLoS ONE,10(10).
MLA Busser B.W.,et al."An orthologous epigenetic gene expression signature derived from differentiating embryonic stem cells identifies regulators of cardiogenesis".PLoS ONE 10.10(2015).
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