Genome-Wide Profiling of Pluripotent Cells Reveals a Unique Molecular Signature of Human Embryonic Germ Cells
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{"title"=>"Genome-wide profiling of pluripotent cells reveals a unique molecular signature of human embryonic germ cells", "type"=>"journal", "authors"=>[{"first_name"=>"Nikta", "last_name"=>"Pashai", "scopus_author_id"=>"55180664900"}, {"first_name"=>"Haiping", "last_name"=>"Hao", "scopus_author_id"=>"50461428300"}, {"first_name"=>"Angelo", "last_name"=>"All", "scopus_author_id"=>"22936834000"}, {"first_name"=>"Siddharth", "last_name"=>"Gupta", "scopus_author_id"=>"55495191600"}, {"first_name"=>"Raghothama", "last_name"=>"Chaerkady", "scopus_author_id"=>"8703517100"}, {"first_name"=>"Alejandro", "last_name"=>"de Los Angeles", "scopus_author_id"=>"23972345500"}, {"first_name"=>"John D.", "last_name"=>"Gearhart", "scopus_author_id"=>"36960096900"}, {"first_name"=>"Candace L.", "last_name"=>"Kerr", "scopus_author_id"=>"7202213885"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-84862642951", "sgr"=>"84862642951", "issn"=>"19326203", "doi"=>"10.1371/journal.pone.0039088", "pmid"=>"22737227", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pui"=>"365066236"}, "id"=>"bdf02025-ab48-34d8-8d67-a76fe7885816", "abstract"=>"Human embryonic germ cells (EGCs) provide a powerful model for identifying molecules involved in the pluripotent state when compared to their progenitors, primordial germ cells (PGCs), and other pluripotent stem cells. Microarray and Principal Component Analysis (PCA) reveals for the first time that human EGCs possess a transcription profile distinct from PGCs and other pluripotent stem cells. Validation with qRT-PCR confirms that human EGCs and PGCs express many pluripotency-associated genes but with quantifiable differences compared to pluripotent embryonic stem cells (ESCs), induced pluripotent stem cells (IPSCs), and embryonal carcinoma cells (ECCs). Analyses also identified a number of target genes that may be potentially associated with their unique pluripotent states. These include IPO7, MED7, RBM26, HSPD1, and KRAS which were upregulated in EGCs along with other pluripotent stem cells when compared to PGCs. Other potential target genes were also found which may contribute toward a primed ESC-like state. These genes were exclusively up-regulated in ESCs, IPSCs and ECCs including PARP1, CCNE1, CDK6, AURKA, MAD2L1, CCNG1, and CCNB1 which are involved in cell cycle regulation, cellular metabolism and DNA repair and replication. Gene classification analysis also confirmed that the distinguishing feature of EGCs compared to ESCs, ECCs, and IPSCs lies primarily in their genetic contribution to cellular metabolism, cell cycle, and cell adhesion. In contrast, several genes were found upregulated in PGCs which may help distinguish their unipotent state including HBA1, DMRT1, SPANXA1, and EHD2. Together, these findings provide the first glimpse into a unique genomic signature of human germ cells and pluripotent stem cells and provide genes potentially involved in defining different states of germ-line pluripotency.", "link"=>"http://www.mendeley.com/research/genomewide-profiling-pluripotent-cells-reveals-unique-molecular-signature-human-embryonic-germ-cells", "reader_count"=>47, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Researcher"=>14, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>20, "Student > Postgraduate"=>3, "Student > Master"=>3, "Student > Bachelor"=>4}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Researcher"=>14, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>20, "Student > Postgraduate"=>3, "Student > Master"=>3, "Student > Bachelor"=>4}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Engineering"=>1, "Biochemistry, Genetics and Molecular Biology"=>8, "Mathematics"=>1, "Agricultural and Biological Sciences"=>32, "Medicine and Dentistry"=>1, "Neuroscience"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Neuroscience"=>{"Neuroscience"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>32}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>8}, "Mathematics"=>{"Mathematics"=>1}, "Unspecified"=>{"Unspecified"=>3}}, "reader_count_by_country"=>{"Sweden"=>1, "United States"=>2, "South Africa"=>1, "France"=>1, "Australia"=>1, "Nepal"=>1}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/620128"], "description"=>"<p><i>OCT4, SOX2, NANOG, and DNMT3B</i> were normalized to the <i>beta-actin</i> gene using the comparative CT method, and plotted relative to the human foreskin fibroblast line, HFF1 (0 baseline) (N  = 3 biological samples with technical triplicates for each cell type, P<0.05). Asterisks denote statistical significant differences in cell lines compared to PGCs.</p>", "links"=>[], "tags"=>["qrt-pcr", "pluripotent", "germ", "genes", "primordial", "cells"], "article_id"=>290608, "categories"=>["Biological Sciences", "Cell Biology", "Developmental Biology"], "users"=>["Nikta Pashai", "Haiping Hao", "Angelo All", "Siddharth Gupta", "Raghothama Chaerkady", "Alejandro De Los Angeles", "John D. Gearhart", "Candace L. Kerr"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0039088.g002", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Real_time_qRT_PCR_analysis_of_several_key_pluripotent_and_germ_cell_associated_genes_in_primordial_germ_cells_and_pluripotent_stem_cells_/290608", "title"=>"Real-time qRT-PCR analysis of several key pluripotent and germ cell associated genes in primordial germ cells and pluripotent stem cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-06-21 00:10:08"}
  • {"files"=>["https://ndownloader.figshare.com/files/620543"], "description"=>"<p>Gene expression levels of (A) PGC signature, (B) EGC and common PGC/EGC signature and (C) ESC, IPSC and ECC group genes are represented in a heat map. Lists of genes corresponding to each group are on the right hand side of the cluster tree. Order of the genes in the tables corresponds to their order in the heat map (high expression in red, log<sup>10</sup> = >1.00; low expression in green; log<sup>10</sup> = <–1.00).</p>", "links"=>[], "tags"=>["clustering"], "article_id"=>291038, "categories"=>["Biological Sciences", "Cell Biology", "Developmental Biology"], "users"=>["Nikta Pashai", "Haiping Hao", "Angelo All", "Siddharth Gupta", "Raghothama Chaerkady", "Alejandro De Los Angeles", "John D. Gearhart", "Candace L. Kerr"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0039088.g005", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Hierarchical_clustering_of_potential_signature_genes_/291038", "title"=>"Hierarchical clustering of potential signature genes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-06-21 00:17:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/619998"], "description"=>"<p>(A) primordial germ cells (PGCs), (B) embryonic germ cells (EGCs), (C) induced pluripotent stem cells (IPSCs), (D) embryonic stem cells (ESCs), and (E) embryonal carcinoma cells (ECCs).</p>", "links"=>[], "tags"=>["images", "cells", "studied"], "article_id"=>290491, "categories"=>["Biological Sciences", "Cell Biology", "Developmental Biology"], "users"=>["Nikta Pashai", "Haiping Hao", "Angelo All", "Siddharth Gupta", "Raghothama Chaerkady", "Alejandro De Los Angeles", "John D. Gearhart", "Candace L. Kerr"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0039088.g001", "stats"=>{"downloads"=>0, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Phase_contrast_images_representing_different_stem_cells_studied_in_gene_expression_analyses_/290491", "title"=>"Phase contrast images representing different stem cells studied in gene expression analyses.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-06-21 00:08:11"}
  • {"files"=>["https://ndownloader.figshare.com/files/620677"], "description"=>"<p>(A) Biological processes up-regulated in ESCs, IPSCs, and ECCs compared to PGCs. (B) Biological processes up-regulated in EGCs compared to PGCs. The allocation of specific biological functions in pluripotent stem cells and EGCs are represented by percentages in the table legend.</p>", "links"=>[], "tags"=>["genes", "molecular"], "article_id"=>291165, "categories"=>["Biological Sciences", "Cell Biology", "Developmental Biology"], "users"=>["Nikta Pashai", "Haiping Hao", "Angelo All", "Siddharth Gupta", "Raghothama Chaerkady", "Alejandro De Los Angeles", "John D. Gearhart", "Candace L. Kerr"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0039088.g006", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Classification_of_genes_by_specific_molecular_and_biological_function_/291165", "title"=>"Classification of genes by specific molecular and biological function.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-06-21 00:19:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/620226"], "description"=>"<p>(A) Two-dimensional PCA map of cell types, comparing PC1 and PC3. (B) Three-dimensional map comparing all cell types. (C) A loading scatter plot for the identification of signature genes. Red dots represent the top 1000 differentially genes expressed across the mean of all lines with FDR adjusted P<0.0001. “PGC signature” genes include <i>HBA1, TEX13,</i> and <i>SPO11</i> located on the lower left half of the scatter plot. In contrast, XIST was upregulated in PGCs compared to other pluripotent stem cell lines as expected given their differentiated state. “PGC/EGC common” genes include <i>H19, BGN, ITGA8, IGFB5, MOV10L1</i>, and <i>TGF-B1</i>. “EGC signature” genes include <i>SOX9, KLF4, FN1, AXL,</i> and <i>FKBP6</i>. “ECC, ESC, and IPSC” signature genes include <i>DPPA4, NANOG, SOX2, PIWIL2, MYCN, GDF3,</i> and <i>OCT4.</i></p>", "links"=>[], "tags"=>["profiles", "primordial", "germ", "cells", "pluripotent"], "article_id"=>290709, "categories"=>["Biological Sciences", "Cell Biology", "Developmental Biology"], "users"=>["Nikta Pashai", "Haiping Hao", "Angelo All", "Siddharth Gupta", "Raghothama Chaerkady", "Alejandro De Los Angeles", "John D. Gearhart", "Candace L. Kerr"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0039088.g003", "stats"=>{"downloads"=>1, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Principal_component_analysis_PCA_of_the_expression_profiles_of_primordial_germ_cells_and_pluripotent_stem_cells_/290709", "title"=>"Principal component analysis (PCA) of the expression profiles of primordial germ cells and pluripotent stem cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-06-21 00:11:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/620949"], "description"=>"<p>Pair-wise comparisons of gene expression profiles.</p>", "links"=>[], "tags"=>["comparisons"], "article_id"=>291441, "categories"=>["Biological Sciences", "Cell Biology", "Developmental Biology"], "users"=>["Nikta Pashai", "Haiping Hao", "Angelo All", "Siddharth Gupta", "Raghothama Chaerkady", "Alejandro De Los Angeles", "John D. Gearhart", "Candace L. Kerr"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0039088.t001", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Pair_wise_comparisons_of_gene_expression_profiles_/291441", "title"=>"Pair-wise comparisons of gene expression profiles.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-06-21 00:24:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/620371"], "description"=>"<p>The vertical axis of each graph shows the log ratio of the expression data relative to the population mean. (A) Genes that are up-regulated in PGCs include (A) <i>SPO11, DMRT1, TEX13, and HBA1.</i> (B) Genes up-regulated in ECCs include <i>SALL4, GDF3, MYCN, and PIWIL2.</i> (C) Genes up-regulated in EGCs include <i>FN1, FKBP6, AXL, and SOX9</i>. (D) Genes up-regulated in IPSCs include <i>MAD2L1, PIK3R3, BAX and APC</i><b>.</b> (E) Genes up-regulated in ESCs include <i>DAZL, CCNG1, JARID2, and ZSCAN1.</i></p>", "links"=>[], "tags"=>["genes"], "article_id"=>290863, "categories"=>["Biological Sciences", "Cell Biology", "Developmental Biology"], "users"=>["Nikta Pashai", "Haiping Hao", "Angelo All", "Siddharth Gupta", "Raghothama Chaerkady", "Alejandro De Los Angeles", "John D. Gearhart", "Candace L. Kerr"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0039088.g004", "stats"=>{"downloads"=>1, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Identification_of_potential_signature_genes_of_PGCs_ECCs_EGCs_IPSCs_and_ESCs_/290863", "title"=>"Identification of potential signature genes of PGCs, ECCs, EGCs, IPSCs, and ESCs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-06-21 00:14:23"}
  • {"files"=>["https://ndownloader.figshare.com/files/322550", "https://ndownloader.figshare.com/files/322567", "https://ndownloader.figshare.com/files/322582", "https://ndownloader.figshare.com/files/322708", "https://ndownloader.figshare.com/files/322746"], "description"=>"<div><p>Human embryonic germ cells (<b>EGCs</b>) provide a powerful model for identifying molecules involved in the pluripotent state when compared to their progenitors, primordial germ cells (<b>PGCs</b>), and other pluripotent stem cells. Microarray and Principal Component Analysis (<b>PCA</b>) reveals for the first time that human EGCs possess a transcription profile distinct from PGCs and other pluripotent stem cells. Validation with qRT-PCR confirms that human EGCs and PGCs express many pluripotency-associated genes but with quantifiable differences compared to pluripotent embryonic stem cells (<b>ESCs</b>), induced pluripotent stem cells (<b>IPSCs</b>), and embryonal carcinoma cells (<b>ECCs</b>). Analyses also identified a number of target genes that may be potentially associated with their unique pluripotent states. These include <em>IPO7</em>, <em>MED7, RBM26, HSPD1</em>, and <em>KRAS</em> which were upregulated in EGCs along with other pluripotent stem cells when compared to PGCs. Other potential target genes were also found which may contribute toward a primed ESC-like state. These genes were exclusively up-regulated in ESCs, IPSCs and ECCs including <em>PARP1, CCNE1, CDK6, AURKA, MAD2L1, CCNG1</em>, and <em>CCNB1</em> which are involved in cell cycle regulation, cellular metabolism and DNA repair and replication. Gene classification analysis also confirmed that the distinguishing feature of EGCs compared to ESCs, ECCs, and IPSCs lies primarily in their genetic contribution to cellular metabolism, cell cycle, and cell adhesion. In contrast, several genes were found upregulated in PGCs which may help distinguish their unipotent state including <em>HBA1, DMRT1, SPANXA1, and EHD2.</em> Together, these findings provide the first glimpse into a unique genomic signature of human germ cells and pluripotent stem cells and provide genes potentially involved in defining different states of germ-line pluripotency.</p> </div>", "links"=>[], "tags"=>["genome-wide", "profiling", "pluripotent", "cells", "reveals", "molecular", "embryonic", "germ"], "article_id"=>123664, "categories"=>["Biological Sciences", "Cell Biology", "Developmental Biology"], "users"=>["Nikta Pashai", "Haiping Hao", "Angelo All", "Siddharth Gupta", "Raghothama Chaerkady", "Alejandro De Los Angeles", "John D. Gearhart", "Candace L. Kerr"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0039088.s001", "https://dx.doi.org/10.1371/journal.pone.0039088.s002", "https://dx.doi.org/10.1371/journal.pone.0039088.s003", "https://dx.doi.org/10.1371/journal.pone.0039088.s004", "https://dx.doi.org/10.1371/journal.pone.0039088.s005"], "stats"=>{"downloads"=>16, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Genome_Wide_Profiling_of_Pluripotent_Cells_Reveals_a_Unique_Molecular_Signature_of_Human_Embryonic_Germ_Cells/123664", "title"=>"Genome-Wide Profiling of Pluripotent Cells Reveals a Unique Molecular Signature of Human Embryonic Germ Cells", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-06-21 01:01:04"}
  • {"files"=>["https://ndownloader.figshare.com/files/620867"], "description"=>"<p>This network is specifically showing genes that are up-regulated in pluripotent stem cells compared to PGCs. Green color represents genes in this network that are highly up-regulated in the ESC, IPSC, and ECC group and gray color represents genes that are expressed in similar levels across all cell types. White signifies that the gene was not detected in the cell lines. Solid and dotted arrows represent direct and indirect interactions, respectively. Elevated levels of <i>KRAS</i> and <i>HSPD1</i> were also detected in EGCs.</p>", "links"=>[], "tags"=>["relationships", "suspected", "genes", "controlling", "dna"], "article_id"=>291357, "categories"=>["Biological Sciences", "Cell Biology", "Developmental Biology"], "users"=>["Nikta Pashai", "Haiping Hao", "Angelo All", "Siddharth Gupta", "Raghothama Chaerkady", "Alejandro De Los Angeles", "John D. Gearhart", "Candace L. Kerr"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0039088.g008", "stats"=>{"downloads"=>3, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Graphical_representation_of_biological_relationships_in_known_or_suspected_genes_associated_with_controlling_cell_cycle_replication_DNA_repair_recombination_and_cell_death_/291357", "title"=>"Graphical representation of biological relationships in known or suspected genes associated with controlling cell cycle, replication, DNA repair, recombination, and cell death.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-06-21 00:22:37"}
  • {"files"=>["https://ndownloader.figshare.com/files/620985"], "description"=>"<p>Classification of genes differentially expressed in ESCs, EGCs, ECCs, and IPSCs versus PGCs.</p>", "links"=>[], "tags"=>["genes", "differentially", "ipscs"], "article_id"=>291470, "categories"=>["Biological Sciences", "Cell Biology", "Developmental Biology"], "users"=>["Nikta Pashai", "Haiping Hao", "Angelo All", "Siddharth Gupta", "Raghothama Chaerkady", "Alejandro De Los Angeles", "John D. Gearhart", "Candace L. Kerr"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0039088.t002", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Classification_of_genes_differentially_expressed_in_ESCs_EGCs_ECCs_and_IPSCs_versus_PGCs_/291470", "title"=>"Classification of genes differentially expressed in ESCs, EGCs, ECCs, and IPSCs versus PGCs.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-06-21 00:24:30"}
  • {"files"=>["https://ndownloader.figshare.com/files/620772"], "description"=>"<p>Green color represents genes of the pathway that are up-regulated in the pluripotent stem cells compared to PGCs and gray color represents genes that are expressed at similar levels between both groups. White signifies genes whose expression was not detected in the cell lines.</p>", "links"=>[], "tags"=>["relationships", "genes", "embryonic", "pluripotency", "ipa"], "article_id"=>291261, "categories"=>["Biological Sciences", "Cell Biology", "Developmental Biology"], "users"=>["Nikta Pashai", "Haiping Hao", "Angelo All", "Siddharth Gupta", "Raghothama Chaerkady", "Alejandro De Los Angeles", "John D. Gearhart", "Candace L. Kerr"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0039088.g007", "stats"=>{"downloads"=>1, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Graphical_representation_of_biological_relationships_in_genes_responsible_for_human_embryonic_stem_cell_pluripotency_detected_by_IPA_analysis_/291261", "title"=>"Graphical representation of biological relationships in genes responsible for human embryonic stem cell pluripotency detected by IPA analysis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-06-21 00:21:01"}

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Relative Metric

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