An Orthologous Epigenetic Gene Expression Signature Derived from Differentiating Embryonic Stem Cells Identifies Regulators of Cardiogenesis
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{"title"=>"An orthologous epigenetic gene expression signature derived from differentiating embryonic stem cells identifies regulators of cardiogenesis", "type"=>"journal", "authors"=>[{"first_name"=>"Brian W.", "last_name"=>"Busser", "scopus_author_id"=>"36965975500"}, {"first_name"=>"Yongshun", "last_name"=>"Lin", "scopus_author_id"=>"7407361185"}, {"first_name"=>"Yanqin", "last_name"=>"Yang", "scopus_author_id"=>"25927628900"}, {"first_name"=>"Jun", "last_name"=>"Zhu", "scopus_author_id"=>"56310977600"}, {"first_name"=>"Guokal", "last_name"=>"Chen", "scopus_author_id"=>"55789887600"}, {"first_name"=>"Alan M.", "last_name"=>"Michelson", "scopus_author_id"=>"35516312800"}], "year"=>2015, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"26485529", "sgr"=>"84949255859", "doi"=>"10.1371/journal.pone.0141066", "scopus"=>"2-s2.0-84949255859", "pui"=>"607132767", "issn"=>"19326203"}, "id"=>"f2da90ca-4f47-36f3-921b-a2c3f1c49fb7", "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.", "link"=>"http://www.mendeley.com/research/orthologous-epigenetic-gene-expression-signature-derived-differentiating-embryonic-stem-cells-identi", "reader_count"=>12, "reader_count_by_academic_status"=>{"Researcher"=>3, "Student > Ph. D. Student"=>3, "Other"=>1, "Student > Master"=>2, "Student > Bachelor"=>2, "Professor"=>1}, "reader_count_by_user_role"=>{"Researcher"=>3, "Student > Ph. D. Student"=>3, "Other"=>1, "Student > Master"=>2, "Student > Bachelor"=>2, "Professor"=>1}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>5, "Agricultural and Biological Sciences"=>6, "Medicine and Dentistry"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>6}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>5}}, "reader_count_by_country"=>{"Germany"=>1}, "group_count"=>2}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2366053"], "description"=>"<p>(A) The distribution of the indicated histone modifications to the genomic region of the mouse and human NKX2-5 gene at the ESC or CP state. Genomic coordinates are indicated for human chromosome 5 (hg19) and mouse chromosome 17 (mm9). Brackets indicate scale of peak. (B) Percentage of indicated genes known to regulate mammalian cardiogenesis. (C) Percentage of indicated cardiogenic genes conserved in <i>Drosophila</i>. (D) Enriched GO categories associated with the indicated genes. * p < 0.0001; **p < 0.0005.</p>", "links"=>[], "tags"=>["cardiogenic pathways", "cell fate decisions", "novel cardiogenic genes", "candidate cardiogenic genes", "candidate genes", "results show", "zinc finger protein 503", "shRNA knockdown", "alternative cell fates", "cardiomyocyte structure", "factor NK 2 homeobox 5", "orthologous gene expression signatures", "gene expression programs", "Differentiating Embryonic Stem Cells Identifies Regulators", "orthologous mouse", "Orthologous Epigenetic Gene Expression Signature Derived", "NK 2 homeobox 5", "gene expression signatures"], "article_id"=>1580417, "categories"=>["Uncategorised"], "users"=>["Brian W. Busser", "Yongshun Lin", "Yanqin Yang", "Jun Zhu", "Guokai Chen", "Alan M. Michelson"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0141066.g001", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_A_multi_species_epigenetic_and_gene_expression_signature_identifies_candidate_cardiogenic_genes_/1580417", "title"=>"A multi-species epigenetic and gene expression signature identifies candidate cardiogenic genes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-10-20 03:13:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/2366065"], "description"=>"<p>Matrix representations of gene expression patterns at different time points of differentiation along the cardiac lineage are shown for WT or shRNA-treated ESCs. (A) Gene expression patterns of mesendodermal (cluster II) and cardiac lineage genes (clusters III, IV, and V) at the indicated time points. (B) Gene expression patterns of the indicated haematopoietic genes at day 10. (C) Gene expression patterns of liver and definitive endodermal genes at the indicated time points.</p>", "links"=>[], "tags"=>["cardiogenic pathways", "cell fate decisions", "novel cardiogenic genes", "candidate cardiogenic genes", "candidate genes", "results show", "zinc finger protein 503", "shRNA knockdown", "alternative cell fates", "cardiomyocyte structure", "factor NK 2 homeobox 5", "orthologous gene expression signatures", "gene expression programs", "Differentiating Embryonic Stem Cells Identifies Regulators", "orthologous mouse", "Orthologous Epigenetic Gene Expression Signature Derived", "NK 2 homeobox 5", "gene expression signatures"], "article_id"=>1580427, "categories"=>["Uncategorised"], "users"=>["Brian W. Busser", "Yongshun Lin", "Yanqin Yang", "Jun Zhu", "Guokai Chen", "Alan M. Michelson"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0141066.g004", "stats"=>{"downloads"=>4, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Transcriptome_analysis_reveals_a_role_for_cardiogenic_TFs_in_activation_of_cardiac_genes_and_repression_of_alternative_cell_fates_/1580427", "title"=>"Transcriptome analysis reveals a role for cardiogenic TFs in activation of cardiac genes and repression of alternative cell fates.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-10-20 03:13:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/2366056"], "description"=>"<p>Stage 16 <i>Drosophila</i> embryos were collected from flies expressing Hand-Gal4, TinD-Gal4, and UAS-dcr2 to flies expressing UAS-RNAi against the indicated gene (with the human ortholog also indicated) or yw (wild-type) and stained with the cardiac markers Tin (green) and Zfh1 (magenta). Genes tested were randomly selected based on public availability of siRNA stocks. Results shown are representative of at least 10 embryos. Embryo images are shown for 5 genes, with the entirety of the Drosophila screen available in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0141066#pone.0141066.s004\" target=\"_blank\">S1 Table</a>. Many siRNA stocks yielded no observable cardiac phenotypes arguing against toxicity of siRNAs creating cardiac phenotypes (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0141066#pone.0141066.s004\" target=\"_blank\">S1 Table</a>).</p>", "links"=>[], "tags"=>["cardiogenic pathways", "cell fate decisions", "novel cardiogenic genes", "candidate cardiogenic genes", "candidate genes", "results show", "zinc finger protein 503", "shRNA knockdown", "alternative cell fates", "cardiomyocyte structure", "factor NK 2 homeobox 5", "orthologous gene expression signatures", "gene expression programs", "Differentiating Embryonic Stem Cells Identifies Regulators", "orthologous mouse", "Orthologous Epigenetic Gene Expression Signature Derived", "NK 2 homeobox 5", "gene expression signatures"], "article_id"=>1580420, "categories"=>["Uncategorised"], "users"=>["Brian W. Busser", "Yongshun Lin", "Yanqin Yang", "Jun Zhu", "Guokai Chen", "Alan M. Michelson"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0141066.g002", "stats"=>{"downloads"=>4, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Screening_orthologs_of_the_mammalian_candidate_genes_in_Drosophila_identifies_regulators_of_heart_development_/1580420", "title"=>"Screening orthologs of the mammalian candidate genes in <i>Drosophila</i> identifies regulators of heart development.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-10-20 03:13:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/2366067", "https://ndownloader.figshare.com/files/2366068", "https://ndownloader.figshare.com/files/2366069", "https://ndownloader.figshare.com/files/2366070", "https://ndownloader.figshare.com/files/2366071"], "description"=>"<div><p>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 <i>Drosophila</i> 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.</p></div>", "links"=>[], "tags"=>["cardiogenic pathways", "cell fate decisions", "novel cardiogenic genes", "candidate cardiogenic genes", "candidate genes", "results show", "zinc finger protein 503", "shRNA knockdown", "alternative cell fates", "cardiomyocyte structure", "factor NK 2 homeobox 5", "orthologous gene expression signatures", "gene expression programs", "Differentiating Embryonic Stem Cells Identifies Regulators", "orthologous mouse", "Orthologous Epigenetic Gene Expression Signature Derived", "NK 2 homeobox 5", "gene expression signatures"], "article_id"=>1580429, "categories"=>["Uncategorised"], "users"=>["Brian W. Busser", "Yongshun Lin", "Yanqin Yang", "Jun Zhu", "Guokai Chen", "Alan M. Michelson"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0141066.s001", "https://dx.doi.org/10.1371/journal.pone.0141066.s002", "https://dx.doi.org/10.1371/journal.pone.0141066.s003", "https://dx.doi.org/10.1371/journal.pone.0141066.s004", "https://dx.doi.org/10.1371/journal.pone.0141066.s005"], "stats"=>{"downloads"=>7, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_An_Orthologous_Epigenetic_Gene_Expression_Signature_Derived_from_Differentiating_Embryonic_Stem_Cells_Identifies_Regulators_of_Cardiogenesis_/1580429", "title"=>"An Orthologous Epigenetic Gene Expression Signature Derived from Differentiating Embryonic Stem Cells Identifies Regulators of Cardiogenesis", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-10-20 03:13:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/2366061"], "description"=>"<p>(A) Flow cytometric analysis of cTnT expression on human ESCs after 10 days of differentiation along the cardiac lineage following shRNA knockdown of the indicated genes. Representative results of five experiments. WT cells were infected with a shRNA targeting GFP or empty vector, which yielded identical results as non-infected cells. (B) Hierarchical clustering of genes showing significant gene expression changes following shRNA knockdown of the indicated genes at the indicated time points. WT = wild-type; ZE = ZEB2 shRNA; ZN = ZNF503 shRNA; NK = NKX2-5 shRNA.</p>", "links"=>[], "tags"=>["cardiogenic pathways", "cell fate decisions", "novel cardiogenic genes", "candidate cardiogenic genes", "candidate genes", "results show", "zinc finger protein 503", "shRNA knockdown", "alternative cell fates", "cardiomyocyte structure", "factor NK 2 homeobox 5", "orthologous gene expression signatures", "gene expression programs", "Differentiating Embryonic Stem Cells Identifies Regulators", "orthologous mouse", "Orthologous Epigenetic Gene Expression Signature Derived", "NK 2 homeobox 5", "gene expression signatures"], "article_id"=>1580425, "categories"=>["Uncategorised"], "users"=>["Brian W. Busser", "Yongshun Lin", "Yanqin Yang", "Jun Zhu", "Guokai Chen", "Alan M. Michelson"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0141066.g003", "stats"=>{"downloads"=>1, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_ZNF503_ZEB2_and_NKX2_5_are_necessary_for_differentiation_of_CMs_from_human_ESCs_/1580425", "title"=>"ZNF503, ZEB2 and NKX2-5 are necessary for differentiation of CMs from human ESCs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-10-20 03:13:01"}

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Relative Metric

{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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