Directed Differentiation of Patient-Specific Induced Pluripotent Stem Cells Identifies the Transcriptional Repression and Epigenetic Modification of NKX2-5, HAND1, and NOTCH1 in Hypoplastic Left Heart Syndrome
Events
Loading … Spinner

Mendeley | Further Information

{"title"=>"Directed differentiation of patient-specific induced pluripotent stem cells identifies the transcriptional repression and epigenetic modification of NKX2-5, HAND1, and NOTCH1 in hypoplastic left heart syndrome", "type"=>"journal", "authors"=>[{"first_name"=>"Junko", "last_name"=>"Kobayashi", "scopus_author_id"=>"56427496600"}, {"first_name"=>"Masashi", "last_name"=>"Yoshida", "scopus_author_id"=>"55480659900"}, {"first_name"=>"Suguru", "last_name"=>"Tarui", "scopus_author_id"=>"56427619100"}, {"first_name"=>"Masataka", "last_name"=>"Hirata", "scopus_author_id"=>"56286774700"}, {"first_name"=>"Yusuke", "last_name"=>"Nagai", "scopus_author_id"=>"14622811000"}, {"first_name"=>"Shingo", "last_name"=>"Kasahara", "scopus_author_id"=>"7102396273"}, {"first_name"=>"Keiji", "last_name"=>"Naruse", "scopus_author_id"=>"7102661918"}, {"first_name"=>"Hiroshi", "last_name"=>"Ito", "scopus_author_id"=>"55488660800"}, {"first_name"=>"Shunji", "last_name"=>"Sano", "scopus_author_id"=>"7201702978"}, {"first_name"=>"Hidemasa", "last_name"=>"Oh", "scopus_author_id"=>"7402326123"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"84904608539", "doi"=>"10.1371/journal.pone.0102796", "pui"=>"373596077", "pmid"=>"25050861", "scopus"=>"2-s2.0-84904608539", "issn"=>"19326203", "isbn"=>"1932-6203"}, "id"=>"afe3f039-5a28-325d-898f-efe882d9777c", "abstract"=>"The genetic basis of hypoplastic left heart syndrome (HLHS) remains unknown, and the lack of animal models to reconstitute the cardiac maldevelopment has hampered the study of this disease. This study investigated the altered control of transcriptional and epigenetic programs that may affect the development of HLHS by using disease-specific induced pluripotent stem (iPS) cells. Cardiac progenitor cells (CPCs) were isolated from patients with congenital heart diseases to generate patient-specific iPS cells. Comparative gene expression analysis of HLHS- and biventricle (BV) heart-derived iPS cells was performed to dissect the complex genetic circuits that may promote the disease phenotype. Both HLHS- and BV heart-derived CPCs were reprogrammed to generate disease-specific iPS cells, which showed characteristic human embryonic stem cell signatures, expressed pluripotency markers, and could give rise to cardiomyocytes. However, HLHS-iPS cells exhibited lower cardiomyogenic differentiation potential than BV-iPS cells. Quantitative gene expression analysis demonstrated that HLHS-derived iPS cells showed transcriptional repression of NKX2-5, reduced levels of TBX2 and NOTCH/HEY signaling, and inhibited HAND1/2 transcripts compared with control cells. Although both HLHS-derived CPCs and iPS cells showed reduced SRE and TNNT2 transcriptional activation compared with BV-derived cells, co-transfection of NKX2-5, HAND1, and NOTCH1 into HLHS-derived cells resulted in synergistic restoration of these promoters activation. Notably, gain- and loss-of-function studies revealed that NKX2-5 had a predominant impact on NPPA transcriptional activation. Moreover, differentiated HLHS-derived iPS cells showed reduced H3K4 dimethylation as well as histone H3 acetylation but increased H3K27 trimethylation to inhibit transcriptional activation on the NKX2-5 promoter. These findings suggest that patient-specific iPS cells may provide molecular insights into complex transcriptional and epigenetic mechanisms, at least in part, through combinatorial expression of NKX2-5, HAND1, and NOTCH1 that coordinately contribute to cardiac malformations in HLHS.", "link"=>"http://www.mendeley.com/research/directed-differentiation-patientspecific-induced-pluripotent-stem-cells-identifies-transcriptional-r", "reader_count"=>22, "reader_count_by_academic_status"=>{"Student > Doctoral Student"=>3, "Researcher"=>5, "Student > Ph. D. Student"=>5, "Student > Postgraduate"=>3, "Student > Master"=>3, "Other"=>1, "Student > Bachelor"=>2}, "reader_count_by_user_role"=>{"Student > Doctoral Student"=>3, "Researcher"=>5, "Student > Ph. D. Student"=>5, "Student > Postgraduate"=>3, "Student > Master"=>3, "Other"=>1, "Student > Bachelor"=>2}, "reader_count_by_subject_area"=>{"Engineering"=>2, "Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>3, "Medicine and Dentistry"=>7, "Agricultural and Biological Sciences"=>7, "Neuroscience"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>2}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>7}, "Neuroscience"=>{"Neuroscience"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>7}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Unspecified"=>{"Unspecified"=>1}}, "group_count"=>0}

Scopus | Further Information

{"@_fa"=>"true", "link"=>[{"@_fa"=>"true", "@ref"=>"self", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/84904608539"}, {"@_fa"=>"true", "@ref"=>"author-affiliation", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/84904608539?field=author,affiliation"}, {"@_fa"=>"true", "@ref"=>"scopus", "@href"=>"https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84904608539&origin=inward"}, {"@_fa"=>"true", "@ref"=>"scopus-citedby", "@href"=>"https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=84904608539&origin=inward"}], "prism:url"=>"https://api.elsevier.com/content/abstract/scopus_id/84904608539", "dc:identifier"=>"SCOPUS_ID:84904608539", "eid"=>"2-s2.0-84904608539", "dc:title"=>"Directed differentiation of patient-specific induced pluripotent stem cells identifies the transcriptional repression and epigenetic modification of NKX2-5, HAND1, and NOTCH1 in hypoplastic left heart syndrome", "dc:creator"=>"Kobayashi J.", "prism:publicationName"=>"PLoS ONE", "prism:eIssn"=>"19326203", "prism:volume"=>"9", "prism:issueIdentifier"=>"7", "prism:pageRange"=>nil, "prism:coverDate"=>"2014-07-22", "prism:coverDisplayDate"=>"22 July 2014", "prism:doi"=>"10.1371/journal.pone.0102796", "citedby-count"=>"19", "affiliation"=>[{"@_fa"=>"true", "affilname"=>"Okayama University", "affiliation-city"=>"Okayama", "affiliation-country"=>"Japan"}], "pubmed-id"=>"25050861", "prism:aggregationType"=>"Journal", "subtype"=>"ar", "subtypeDescription"=>"Article", "article-number"=>"e102796", "source-id"=>"10600153309", "openaccess"=>"1", "openaccessFlag"=>true}

Facebook

  • {"url"=>"http%3A%2F%2Fjournals.plos.org%2Fplosone%2Farticle%3Fid%3D10.1371%252Fjournal.pone.0102796", "share_count"=>0, "like_count"=>0, "comment_count"=>0, "click_count"=>0, "total_count"=>0}

Counter

  • {"month"=>"7", "year"=>"2014", "pdf_views"=>"78", "xml_views"=>"7", "html_views"=>"189"}
  • {"month"=>"8", "year"=>"2014", "pdf_views"=>"36", "xml_views"=>"2", "html_views"=>"98"}
  • {"month"=>"9", "year"=>"2014", "pdf_views"=>"40", "xml_views"=>"1", "html_views"=>"110"}
  • {"month"=>"10", "year"=>"2014", "pdf_views"=>"31", "xml_views"=>"1", "html_views"=>"94"}
  • {"month"=>"11", "year"=>"2014", "pdf_views"=>"15", "xml_views"=>"2", "html_views"=>"76"}
  • {"month"=>"12", "year"=>"2014", "pdf_views"=>"15", "xml_views"=>"1", "html_views"=>"66"}
  • {"month"=>"1", "year"=>"2015", "pdf_views"=>"22", "xml_views"=>"0", "html_views"=>"98"}
  • {"month"=>"2", "year"=>"2015", "pdf_views"=>"18", "xml_views"=>"0", "html_views"=>"53"}
  • {"month"=>"3", "year"=>"2015", "pdf_views"=>"23", "xml_views"=>"0", "html_views"=>"58"}
  • {"month"=>"4", "year"=>"2015", "pdf_views"=>"11", "xml_views"=>"1", "html_views"=>"43"}
  • {"month"=>"5", "year"=>"2015", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"41"}
  • {"month"=>"6", "year"=>"2015", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"33"}
  • {"month"=>"7", "year"=>"2015", "pdf_views"=>"15", "xml_views"=>"0", "html_views"=>"26"}
  • {"month"=>"8", "year"=>"2015", "pdf_views"=>"17", "xml_views"=>"0", "html_views"=>"40"}
  • {"month"=>"9", "year"=>"2015", "pdf_views"=>"6", "xml_views"=>"1", "html_views"=>"47"}
  • {"month"=>"10", "year"=>"2015", "pdf_views"=>"12", "xml_views"=>"1", "html_views"=>"29"}
  • {"month"=>"11", "year"=>"2015", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"39"}
  • {"month"=>"12", "year"=>"2015", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"46"}
  • {"month"=>"1", "year"=>"2016", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"29"}
  • {"month"=>"2", "year"=>"2016", "pdf_views"=>"1", "xml_views"=>"0", "html_views"=>"27"}
  • {"month"=>"3", "year"=>"2016", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"38"}
  • {"month"=>"4", "year"=>"2016", "pdf_views"=>"23", "xml_views"=>"0", "html_views"=>"39"}
  • {"month"=>"5", "year"=>"2016", "pdf_views"=>"16", "xml_views"=>"0", "html_views"=>"41"}
  • {"month"=>"6", "year"=>"2016", "pdf_views"=>"16", "xml_views"=>"0", "html_views"=>"34"}
  • {"month"=>"7", "year"=>"2016", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"28"}
  • {"month"=>"8", "year"=>"2016", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"16"}
  • {"month"=>"9", "year"=>"2016", "pdf_views"=>"15", "xml_views"=>"0", "html_views"=>"28"}
  • {"month"=>"10", "year"=>"2016", "pdf_views"=>"16", "xml_views"=>"0", "html_views"=>"43"}
  • {"month"=>"11", "year"=>"2016", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"35"}
  • {"month"=>"12", "year"=>"2016", "pdf_views"=>"28", "xml_views"=>"1", "html_views"=>"38"}
  • {"month"=>"1", "year"=>"2017", "pdf_views"=>"18", "xml_views"=>"2", "html_views"=>"52"}
  • {"month"=>"2", "year"=>"2017", "pdf_views"=>"5", "xml_views"=>"1", "html_views"=>"38"}
  • {"month"=>"3", "year"=>"2017", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"44"}
  • {"month"=>"4", "year"=>"2017", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"39"}
  • {"month"=>"5", "year"=>"2017", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"24"}
  • {"month"=>"6", "year"=>"2017", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"33"}
  • {"month"=>"7", "year"=>"2017", "pdf_views"=>"13", "xml_views"=>"3", "html_views"=>"34"}
  • {"month"=>"8", "year"=>"2017", "pdf_views"=>"5", "xml_views"=>"1", "html_views"=>"18"}
  • {"month"=>"9", "year"=>"2017", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"39"}
  • {"month"=>"10", "year"=>"2017", "pdf_views"=>"9", "xml_views"=>"1", "html_views"=>"45"}
  • {"month"=>"11", "year"=>"2017", "pdf_views"=>"5", "xml_views"=>"1", "html_views"=>"75"}
  • {"month"=>"12", "year"=>"2017", "pdf_views"=>"11", "xml_views"=>"2", "html_views"=>"52"}
  • {"month"=>"1", "year"=>"2018", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"78"}
  • {"month"=>"2", "year"=>"2018", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"32"}
  • {"month"=>"3", "year"=>"2018", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"10"}
  • {"month"=>"4", "year"=>"2018", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"24"}
  • {"month"=>"5", "year"=>"2018", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"18"}
  • {"month"=>"6", "year"=>"2018", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"8"}
  • {"month"=>"7", "year"=>"2018", "pdf_views"=>"7", "xml_views"=>"3", "html_views"=>"9"}
  • {"month"=>"8", "year"=>"2018", "pdf_views"=>"1", "xml_views"=>"1", "html_views"=>"10"}
  • {"month"=>"9", "year"=>"2018", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"24"}
  • {"month"=>"10", "year"=>"2018", "pdf_views"=>"14", "xml_views"=>"2", "html_views"=>"23"}
  • {"month"=>"11", "year"=>"2018", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"9"}
  • {"month"=>"12", "year"=>"2018", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"11"}
  • {"month"=>"1", "year"=>"2019", "pdf_views"=>"10", "xml_views"=>"1", "html_views"=>"42"}
  • {"month"=>"2", "year"=>"2019", "pdf_views"=>"20", "xml_views"=>"0", "html_views"=>"16"}
  • {"month"=>"3", "year"=>"2019", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"10"}
  • {"month"=>"4", "year"=>"2019", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"15"}
  • {"month"=>"5", "year"=>"2019", "pdf_views"=>"10", "xml_views"=>"1", "html_views"=>"14"}

Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1605438"], "description"=>"<p>(A) Representative images of alkaline phosphatase staining are shown for iPS cells generated from HLHS (iPS30) and TAPVC representing BV (iPS65) patients. Bar, 200 µm. (B) Chromosomal abnormalities were not found in both iPS clones at 10 weeks by the G-banding method. (C) Heat map (right) and hierarchical cluster analysis (left) of global gene expression from patient-specific CPCs and iPS clones are shown. A commercially available 201B7 clone (Riken) was used as control human iPS cells.</p>", "links"=>[], "tags"=>["anatomy", "Cardiovascular anatomy", "cell biology", "Cellular types", "Animal cells", "stem cells", "Induced pluripotent stem cells", "Molecular cell biology", "developmental biology", "Cell differentiation", "Cell fate determination", "genetics", "gene expression", "cardiology", "Pediatric cardiology", "pediatrics", "Surgical and invasive medical procedures", "Cardiothoracic surgery", "cpcs"], "article_id"=>1114656, "categories"=>["Biological Sciences"], "users"=>["Junko Kobayashi", "Masashi Yoshida", "Suguru Tarui", "Masataka Hirata", "Yusuke Nagai", "Shingo Kasahara", "Keiji Naruse", "Hiroshi Ito", "Shunji Sano", "Hidemasa Oh"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0102796.g003", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Patient_specific_CPCs_were_fully_reprogrammed_/1114656", "title"=>"Patient-specific CPCs were fully reprogrammed.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-22 03:14:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/1605450"], "description"=>"<p>Undifferentiated CPCs (A) and iPS cells (B) and differentiated (cardiac-lineage induction for 3 weeks) iPS cells (C) were analyzed by ChIP assay. N.D., not detected; *, p<0.05 vs. differentiated BV-derived iPS cells. Data are expressed as the percentage of input DNA.</p>", "links"=>[], "tags"=>["anatomy", "Cardiovascular anatomy", "cell biology", "Cellular types", "Animal cells", "stem cells", "Induced pluripotent stem cells", "Molecular cell biology", "developmental biology", "Cell differentiation", "Cell fate determination", "genetics", "gene expression", "cardiology", "Pediatric cardiology", "pediatrics", "Surgical and invasive medical procedures", "Cardiothoracic surgery", "cell-derived", "cardiomyocytes", "showed", "suppressed", "h3k4", "methylation", "h3", "h3k27"], "article_id"=>1114668, "categories"=>["Biological Sciences"], "users"=>["Junko Kobayashi", "Masashi Yoshida", "Suguru Tarui", "Masataka Hirata", "Yusuke Nagai", "Shingo Kasahara", "Keiji Naruse", "Hiroshi Ito", "Shunji Sano", "Hidemasa Oh"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0102796.g008", "stats"=>{"downloads"=>3, "page_views"=>29, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_HLHS_iPS_cell_derived_cardiomyocytes_showed_suppressed_H3K4_methylation_and_H3_acetylation_but_increased_H3K27_methylation_/1114668", "title"=>"HLHS-iPS cell-derived cardiomyocytes showed suppressed H3K4 methylation and H3 acetylation, but increased H3K27 methylation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-22 03:14:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/1605447"], "description"=>"<p>mRNA expressions in control 201B7 iPS cells and one BV- and two HLHS-derived iPS cell lines during cardiac lineage induction at respective time points were determined by quantitative RT-PCR. All data were obtained from more than five independent experiments with three different clonal derivatives and normalized using β2-microglobulin and human heart tissue for comparisons. *, p<0.05 vs. differentiated 201B7 and BV-derived iPS cells at corresponding time points. †, p<0.05 vs. 201B7 at corresponding time points.</p>", "links"=>[], "tags"=>["anatomy", "Cardiovascular anatomy", "cell biology", "Cellular types", "Animal cells", "stem cells", "Induced pluripotent stem cells", "Molecular cell biology", "developmental biology", "Cell differentiation", "Cell fate determination", "genetics", "gene expression", "cardiology", "Pediatric cardiology", "pediatrics", "Surgical and invasive medical procedures", "Cardiothoracic surgery", "cell-derived", "cardiomyocytes", "showed", "cardiac"], "article_id"=>1114665, "categories"=>["Biological Sciences"], "users"=>["Junko Kobayashi", "Masashi Yoshida", "Suguru Tarui", "Masataka Hirata", "Yusuke Nagai", "Shingo Kasahara", "Keiji Naruse", "Hiroshi Ito", "Shunji Sano", "Hidemasa Oh"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0102796.g006", "stats"=>{"downloads"=>2, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_HLHS_iPS_cell_derived_cardiomyocytes_showed_decreased_cardiac_transcripts_/1114665", "title"=>"HLHS-iPS cell-derived cardiomyocytes showed decreased cardiac transcripts.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-22 03:14:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/1605446"], "description"=>"<p>(A) Both HLHS- and BV-derived iPS cells could generate cardiac troponin-T (TNNT2)-positive cardiomyocytes (green) 3 weeks after lineage induction. Nuclei were shown by DAPI (blue). Bar, 30 µm. (B) Time course of TNNT2 expression in disease-specific iPS cells. Data were normalized using β2-microglobulin and human heart tissue for comparisons. *, p<0.05 vs. control and differentiated BV-derived iPS cells at 3 weeks. †, p<0.05 vs. before cardiac lineage induction (0 weeks) in each group.</p>", "links"=>[], "tags"=>["anatomy", "Cardiovascular anatomy", "cell biology", "Cellular types", "Animal cells", "stem cells", "Induced pluripotent stem cells", "Molecular cell biology", "developmental biology", "Cell differentiation", "Cell fate determination", "genetics", "gene expression", "cardiology", "Pediatric cardiology", "pediatrics", "Surgical and invasive medical procedures", "Cardiothoracic surgery", "ips", "cells"], "article_id"=>1114664, "categories"=>["Biological Sciences"], "users"=>["Junko Kobayashi", "Masashi Yoshida", "Suguru Tarui", "Masataka Hirata", "Yusuke Nagai", "Shingo Kasahara", "Keiji Naruse", "Hiroshi Ito", "Shunji Sano", "Hidemasa Oh"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0102796.g005", "stats"=>{"downloads"=>1, "page_views"=>26, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_HLHS_derived_iPS_cells_could_give_rise_to_cardiomyocytes_/1114664", "title"=>"HLHS-derived iPS cells could give rise to cardiomyocytes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-22 03:14:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/1605454"], "description"=>"<p>(A) Core transcriptional factors expressed in cardiac progenitor cells serve as targets in response to inductive signals to initiate cardiogenesis. NKX2-5 is predominantly expressed in the primary heart field and controls progenitor cell proliferation. Genes regulate atrioventricular (AV) canal and valve development. Reduced expression may contribute to mitral- and aortic-valve stenosis/atresia often seen in HLHS. NOCTH modulates left heart outflow tract development and the resultant obstruction may cause secondary ventricle hypoplasia. HAND1/2 specify left and right ventricular chamber morphogenesis, and the absence of these genes may lead to a hypoplastic ventricle. (B–D) Schematic diagrams of <i>SRE</i>, <i>TNNT2</i>, and <i>NPPA</i> transcriptional activation. HLHS-derived CPCs and iPS cells showed significantly reduced luciferase activities compared with BV-derived cells. Co-transfection analysis of reporter constructs with NKX2-5, HAND1, and NOTCH1, proposed core transcriptional factors, could synergistically restore the transcriptional activation in these reporters equivalent to the levels in BV-derived cells. (E) Major chromatin features in differentiated HLHS- and BV-derived iPS cells are shown. Upon cardiomyocyte differentiation, HLHS-derived iPS cells failed to enrich the active histone marks such as H3K4me2 and acH3, whereas repressive histone marks such as H3K27me3 increased, resulting in compact chromatin that lost enhancer marks and gained repressor marks on the <i>NKX2-5</i> promoter.</p>", "links"=>[], "tags"=>["anatomy", "Cardiovascular anatomy", "cell biology", "Cellular types", "Animal cells", "stem cells", "Induced pluripotent stem cells", "Molecular cell biology", "developmental biology", "Cell differentiation", "Cell fate determination", "genetics", "gene expression", "cardiology", "Pediatric cardiology", "pediatrics", "Surgical and invasive medical procedures", "Cardiothoracic surgery"], "article_id"=>1114672, "categories"=>["Biological Sciences"], "users"=>["Junko Kobayashi", "Masashi Yoshida", "Suguru Tarui", "Masataka Hirata", "Yusuke Nagai", "Shingo Kasahara", "Keiji Naruse", "Hiroshi Ito", "Shunji Sano", "Hidemasa Oh"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0102796.g009", "stats"=>{"downloads"=>3, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Orchestrated_gene_regulatory_network_in_the_development_of_HLHS_/1114672", "title"=>"Orchestrated gene regulatory network in the development of HLHS.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-22 03:14:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/1605434"], "description"=>"<p>(A) Schematic presentation of CPC isolation and iPS generation. (B) Retroviral transduction was verified by tagged-PCR and endogenous genes (C) are shown. (D) Retroviral silencing was confirmed during reprogramming after 3 months of infection. Trans- and endogenous-gene expressions are shown.</p>", "links"=>[], "tags"=>["anatomy", "Cardiovascular anatomy", "cell biology", "Cellular types", "Animal cells", "stem cells", "Induced pluripotent stem cells", "Molecular cell biology", "developmental biology", "Cell differentiation", "Cell fate determination", "genetics", "gene expression", "cardiology", "Pediatric cardiology", "pediatrics", "Surgical and invasive medical procedures", "Cardiothoracic surgery", "disease-specific"], "article_id"=>1114652, "categories"=>["Biological Sciences"], "users"=>["Junko Kobayashi", "Masashi Yoshida", "Suguru Tarui", "Masataka Hirata", "Yusuke Nagai", "Shingo Kasahara", "Keiji Naruse", "Hiroshi Ito", "Shunji Sano", "Hidemasa Oh"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0102796.g001", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Reprogramming_of_disease_specific_CPCs_/1114652", "title"=>"Reprogramming of disease-specific CPCs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-22 03:14:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/1605448"], "description"=>"<p>Transcriptional activation of <i>SRE</i> promoter luciferase construct by combinatorial transfection of NKX2-5, HAND1, and NOTCH1 in HLHS- and BV-derived CPCs (A) or iPS cells (B). Co-transfection of <i>TNNT2</i> luciferase reporter with NKX2-5, HAND1, and NOTCH1 in CPCs (C) or iPS cells (D) is shown. <i>NPPA</i> luciferase construct was co-transfected with NKX2-5, HAND1, and NOTCH1 alone or in combination into CPCs (E) or iPS cells (F). (G-I) BV-derived CPCs were transfected with either control or shRNAs specific to inhibit NKX2-5, HAND1, and NOTCH1 expression. Results were normalized using an internal control (SEAP or hRluc) and obtained from more than triplicate sets of experiments. *, p<0.05 vs. the same HLHS sample without transfection of the gene of interest. †, p<0.05 vs. BV sample transfected with control vector alone. ‡, p<0.05 vs. both HLHS samples with the same treatment. §, p<0.01 vs. BV sample transfected with control vector alone.</p>", "links"=>[], "tags"=>["anatomy", "Cardiovascular anatomy", "cell biology", "Cellular types", "Animal cells", "stem cells", "Induced pluripotent stem cells", "Molecular cell biology", "developmental biology", "Cell differentiation", "Cell fate determination", "genetics", "gene expression", "cardiology", "Pediatric cardiology", "pediatrics", "Surgical and invasive medical procedures", "Cardiothoracic surgery", "restoration", "promoters", "hlhs-derived", "cpcs", "ips"], "article_id"=>1114666, "categories"=>["Biological Sciences"], "users"=>["Junko Kobayashi", "Masashi Yoshida", "Suguru Tarui", "Masataka Hirata", "Yusuke Nagai", "Shingo Kasahara", "Keiji Naruse", "Hiroshi Ito", "Shunji Sano", "Hidemasa Oh"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0102796.g007", "stats"=>{"downloads"=>4, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Synergistic_restoration_of_target_promoters_by_NKX2_5_HAND1_and_NOTCH_in_HLHS_derived_CPCs_and_iPS_cells_/1114666", "title"=>"Synergistic restoration of target promoters by <i>NKX2-5</i>, <i>HAND1</i>, and <i>NOTCH</i> in HLHS-derived CPCs and iPS cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-22 03:14:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/1605442"], "description"=>"<p>Gross morphology and hematoxylin and eosin staining of patient-specific iPS cell-derived teratomas are shown. Teratomas were found in the testes of NOD/SCID mice 10 to 12 weeks after transplantation. Histological sections of identified cells represent all three germ layers. Bar, 50 µm.</p>", "links"=>[], "tags"=>["anatomy", "Cardiovascular anatomy", "cell biology", "Cellular types", "Animal cells", "stem cells", "Induced pluripotent stem cells", "Molecular cell biology", "developmental biology", "Cell differentiation", "Cell fate determination", "genetics", "gene expression", "cardiology", "Pediatric cardiology", "pediatrics", "Surgical and invasive medical procedures", "Cardiothoracic surgery", "ips", "cells", "differentiated", "germ", "origins"], "article_id"=>1114660, "categories"=>["Biological Sciences"], "users"=>["Junko Kobayashi", "Masashi Yoshida", "Suguru Tarui", "Masataka Hirata", "Yusuke Nagai", "Shingo Kasahara", "Keiji Naruse", "Hiroshi Ito", "Shunji Sano", "Hidemasa Oh"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0102796.g004", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Patient_derived_iPS_cells_differentiated_into_all_three_germ_layer_origins_in_vivo_/1114660", "title"=>"Patient-derived iPS cells differentiated into all three germ layer origins <i>in vivo</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-22 03:14:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/1605456"], "description"=>"<div><p>The genetic basis of hypoplastic left heart syndrome (HLHS) remains unknown, and the lack of animal models to reconstitute the cardiac maldevelopment has hampered the study of this disease. This study investigated the altered control of transcriptional and epigenetic programs that may affect the development of HLHS by using disease-specific induced pluripotent stem (iPS) cells. Cardiac progenitor cells (CPCs) were isolated from patients with congenital heart diseases to generate patient-specific iPS cells. Comparative gene expression analysis of HLHS- and biventricle (BV) heart-derived iPS cells was performed to dissect the complex genetic circuits that may promote the disease phenotype. Both HLHS- and BV heart-derived CPCs were reprogrammed to generate disease-specific iPS cells, which showed characteristic human embryonic stem cell signatures, expressed pluripotency markers, and could give rise to cardiomyocytes. However, HLHS-iPS cells exhibited lower cardiomyogenic differentiation potential than BV-iPS cells. Quantitative gene expression analysis demonstrated that HLHS-derived iPS cells showed transcriptional repression of NKX2-5, reduced levels of TBX2 and NOTCH/HEY signaling, and inhibited HAND1/2 transcripts compared with control cells. Although both HLHS-derived CPCs and iPS cells showed reduced <i>SRE</i> and <i>TNNT2</i> transcriptional activation compared with BV-derived cells, co-transfection of NKX2-5, HAND1, and NOTCH1 into HLHS-derived cells resulted in synergistic restoration of these promoters activation. Notably, gain- and loss-of-function studies revealed that NKX2-5 had a predominant impact on <i>NPPA</i> transcriptional activation. Moreover, differentiated HLHS-derived iPS cells showed reduced H3K4 dimethylation as well as histone H3 acetylation but increased H3K27 trimethylation to inhibit transcriptional activation on the <i>NKX2-5</i> promoter. These findings suggest that patient-specific iPS cells may provide molecular insights into complex transcriptional and epigenetic mechanisms, at least in part, through combinatorial expression of NKX2-5, HAND1, and NOTCH1 that coordinately contribute to cardiac malformations in HLHS.</p></div>", "links"=>[], "tags"=>["anatomy", "Cardiovascular anatomy", "cell biology", "Cellular types", "Animal cells", "stem cells", "Induced pluripotent stem cells", "Molecular cell biology", "developmental biology", "Cell differentiation", "Cell fate determination", "genetics", "gene expression", "cardiology", "Pediatric cardiology", "pediatrics", "Surgical and invasive medical procedures", "Cardiothoracic surgery", "differentiation", "patient-specific", "induced", "pluripotent", "cells", "identifies", "transcriptional", "repression", "epigenetic", "modification", "notch1", "hypoplastic"], "article_id"=>1114674, "categories"=>["Biological Sciences"], "users"=>["Junko Kobayashi", "Masashi Yoshida", "Suguru Tarui", "Masataka Hirata", "Yusuke Nagai", "Shingo Kasahara", "Keiji Naruse", "Hiroshi Ito", "Shunji Sano", "Hidemasa Oh"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0102796", "stats"=>{"downloads"=>11, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Directed_Differentiation_of_Patient_Specific_Induced_Pluripotent_Stem_Cells_Identifies_the_Transcriptional_Repression_and_Epigenetic_Modification_of_NKX2_5_HAND1_and_NOTCH1_in_Hypoplastic_Left_Heart_Syndrome_/1114674", "title"=>"Directed Differentiation of Patient-Specific Induced Pluripotent Stem Cells Identifies the Transcriptional Repression and Epigenetic Modification of NKX2-5, HAND1, and NOTCH1 in Hypoplastic Left Heart Syndrome", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-07-22 03:14:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/1605437"], "description"=>"<p>Representative patient-specific iPS clones at passage 10 (A, iPS30: HLHS; B, iPS65: TAPVC, representing BV). Colonies were stained with transcription factors typically expressed in iPS cells. Bar, 200 µm. (C and D) Bisulfite sequencing analysis of <i>OCT4</i> and <i>NANOG</i> promoter regions during reprogramming is shown. Closed and open circles represent methylated and unmethylated CpG dinucleotides, respectively.</p>", "links"=>[], "tags"=>["anatomy", "Cardiovascular anatomy", "cell biology", "Cellular types", "Animal cells", "stem cells", "Induced pluripotent stem cells", "Molecular cell biology", "developmental biology", "Cell differentiation", "Cell fate determination", "genetics", "gene expression", "cardiology", "Pediatric cardiology", "pediatrics", "Surgical and invasive medical procedures", "Cardiothoracic surgery", "disease-specific", "ips"], "article_id"=>1114655, "categories"=>["Biological Sciences"], "users"=>["Junko Kobayashi", "Masashi Yoshida", "Suguru Tarui", "Masataka Hirata", "Yusuke Nagai", "Shingo Kasahara", "Keiji Naruse", "Hiroshi Ito", "Shunji Sano", "Hidemasa Oh"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0102796.g002", "stats"=>{"downloads"=>1, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Characterization_of_disease_specific_iPS_cells_/1114655", "title"=>"Characterization of disease-specific iPS cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-22 03:14:58"}

PMC Usage Stats | Further Information

  • {"unique-ip"=>"29", "full-text"=>"32", "pdf"=>"10", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"4"}
  • {"unique-ip"=>"23", "full-text"=>"25", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"8", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"5"}
  • {"unique-ip"=>"23", "full-text"=>"26", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2015", "month"=>"6"}
  • {"unique-ip"=>"21", "full-text"=>"15", "pdf"=>"11", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"13", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2015", "month"=>"7"}
  • {"unique-ip"=>"31", "full-text"=>"23", "pdf"=>"17", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"3"}
  • {"unique-ip"=>"16", "full-text"=>"13", "pdf"=>"13", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"9", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"2"}
  • {"unique-ip"=>"22", "full-text"=>"29", "pdf"=>"11", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"8"}
  • {"unique-ip"=>"18", "full-text"=>"13", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"9", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"9"}
  • {"unique-ip"=>"25", "full-text"=>"24", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"11", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2015", "month"=>"10"}
  • {"unique-ip"=>"32", "full-text"=>"29", "pdf"=>"14", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"14", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"7"}
  • {"unique-ip"=>"53", "full-text"=>"47", "pdf"=>"26", "abstract"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"12", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"8"}
  • {"unique-ip"=>"51", "full-text"=>"37", "pdf"=>"22", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"20", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2014", "month"=>"9"}
  • {"unique-ip"=>"52", "full-text"=>"46", "pdf"=>"27", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"19", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2014", "month"=>"10"}
  • {"unique-ip"=>"11", "full-text"=>"9", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"2"}
  • {"unique-ip"=>"31", "full-text"=>"28", "pdf"=>"19", "abstract"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"11"}
  • {"unique-ip"=>"17", "full-text"=>"14", "pdf"=>"12", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"12"}
  • {"unique-ip"=>"33", "full-text"=>"25", "pdf"=>"22", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2015", "month"=>"1"}
  • {"unique-ip"=>"23", "full-text"=>"18", "pdf"=>"11", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2015", "month"=>"11"}
  • {"unique-ip"=>"19", "full-text"=>"17", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"12"}
  • {"unique-ip"=>"18", "full-text"=>"18", "pdf"=>"12", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"1"}
  • {"unique-ip"=>"13", "full-text"=>"10", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"13", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2016", "month"=>"3"}
  • {"unique-ip"=>"10", "full-text"=>"9", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"4"}
  • {"unique-ip"=>"19", "full-text"=>"20", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"11", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"5"}
  • {"unique-ip"=>"8", "full-text"=>"6", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"6"}
  • {"unique-ip"=>"18", "full-text"=>"16", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"11", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"7"}
  • {"unique-ip"=>"13", "full-text"=>"13", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"8"}
  • {"unique-ip"=>"11", "full-text"=>"12", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2016", "month"=>"9"}
  • {"unique-ip"=>"21", "full-text"=>"26", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"10"}
  • {"unique-ip"=>"12", "full-text"=>"9", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"10", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2016", "month"=>"11"}
  • {"unique-ip"=>"19", "full-text"=>"24", "pdf"=>"11", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"8", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"12"}
  • {"unique-ip"=>"21", "full-text"=>"26", "pdf"=>"14", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"1"}
  • {"unique-ip"=>"16", "full-text"=>"19", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"2"}
  • {"unique-ip"=>"10", "full-text"=>"9", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"18", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2017", "month"=>"3"}
  • {"unique-ip"=>"14", "full-text"=>"16", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"4"}
  • {"unique-ip"=>"23", "full-text"=>"23", "pdf"=>"12", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"5"}
  • {"unique-ip"=>"10", "full-text"=>"10", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"16", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2017", "month"=>"6"}
  • {"unique-ip"=>"12", "full-text"=>"11", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"7"}
  • {"unique-ip"=>"13", "full-text"=>"16", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"8"}
  • {"unique-ip"=>"9", "full-text"=>"8", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"9", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"9"}
  • {"unique-ip"=>"14", "full-text"=>"11", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"10"}
  • {"unique-ip"=>"17", "full-text"=>"19", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"16", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"11"}
  • {"unique-ip"=>"14", "full-text"=>"13", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2017", "month"=>"12"}
  • {"unique-ip"=>"14", "full-text"=>"20", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2018", "month"=>"1"}
  • {"unique-ip"=>"12", "full-text"=>"11", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"17", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"3"}
  • {"unique-ip"=>"26", "full-text"=>"27", "pdf"=>"10", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2019", "month"=>"1"}
  • {"unique-ip"=>"12", "full-text"=>"13", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"10", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
  • {"unique-ip"=>"17", "full-text"=>"15", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2018", "month"=>"11"}
  • {"unique-ip"=>"12", "full-text"=>"14", "pdf"=>"7", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"4"}
  • {"unique-ip"=>"15", "full-text"=>"21", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2018", "month"=>"5"}
  • {"unique-ip"=>"10", "full-text"=>"9", "pdf"=>"6", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"6"}
  • {"unique-ip"=>"11", "full-text"=>"11", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2018", "month"=>"7"}
  • {"unique-ip"=>"6", "full-text"=>"4", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"11", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"8"}
  • {"unique-ip"=>"12", "full-text"=>"11", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"10"}
  • {"unique-ip"=>"8", "full-text"=>"8", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2018", "month"=>"9"}
  • {"unique-ip"=>"10", "full-text"=>"11", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"11", "full-text"=>"11", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"12", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"9", "full-text"=>"12", "pdf"=>"6", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}

Relative Metric

{"start_date"=>"2014-01-01T00:00:00Z", "end_date"=>"2014-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences/Biochemistry", "average_usage"=>[282]}, {"subject_area"=>"/Biology and life sciences/Developmental biology", "average_usage"=>[285]}, {"subject_area"=>"/Medicine and health sciences", "average_usage"=>[285]}]}
Loading … Spinner
There are currently no alerts