Early reprogramming regulators identified by prospective isolation and mass cytometry View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-04-01

AUTHORS

Ernesto Lujan, Eli R. Zunder, Yi Han Ng, Isabel N. Goronzy, Garry P. Nolan, Marius Wernig

ABSTRACT

In the context of most induced pluripotent stem (iPS) cell reprogramming methods, heterogeneous populations of non-productive and staggered productive intermediates arise at different reprogramming time points. Despite recent reports claiming substantially increased reprogramming efficiencies using genetically modified donor cells, prospectively isolating distinct reprogramming intermediates remains an important goal to decipher reprogramming mechanisms. Previous attempts to identify surface markers of intermediate cell populations were based on the assumption that, during reprogramming, cells progressively lose donor cell identity and gradually acquire iPS cell properties. Here we report that iPS cell and epithelial markers, such as SSEA1 and EpCAM, respectively, are not predictive of reprogramming during early phases. Instead, in a systematic functional surface marker screen, we find that early reprogramming-prone cells express a unique set of surface markers, including CD73, CD49d and CD200, that are absent in both fibroblasts and iPS cells. Single-cell mass cytometry and prospective isolation show that these distinct intermediates are transient and bridge the gap between donor cell silencing and pluripotency marker acquisition during the early, presumably stochastic, reprogramming phase. Expression profiling reveals early upregulation of the transcriptional regulators Nr0b1 and Etv5 in this reprogramming state, preceding activation of key pluripotency regulators such as Rex1 (also known as Zfp42), Dppa2, Nanog and Sox2. Both factors are required for the generation of the early intermediate state and fully reprogrammed iPS cells, and thus represent some of the earliest known regulators of iPS cell induction. Our study deconvolutes the first steps in a hierarchical series of events that lead to pluripotency acquisition. More... »

PAGES

352

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nature14274

DOI

http://dx.doi.org/10.1038/nature14274

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1052594762

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/25830878


Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
Incoming Citations Browse incoming citations for this publication using opencitations.net

JSON-LD is the canonical representation for SciGraph data.

TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

[
  {
    "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
    "about": [
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/0601", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Biochemistry and Cell Biology", 
        "type": "DefinedTerm"
      }, 
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/06", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Biological Sciences", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "5'-Nucleotidase", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Animals", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Antigens, CD", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Antigens, Neoplasm", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Biomarkers", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Cell Adhesion Molecules", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Cell Separation", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Cellular Reprogramming", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "DAX-1 Orphan Nuclear Receptor", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "DNA-Binding Proteins", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Epithelial Cell Adhesion Molecule", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Epithelial Cells", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Fibroblasts", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Flow Cytometry", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Gene Expression Profiling", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Homeodomain Proteins", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Induced Pluripotent Stem Cells", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Integrin alpha4", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Lewis X Antigen", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Mice", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Nanog Homeobox Protein", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Nuclear Proteins", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "SOXB1 Transcription Factors", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Time Factors", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Transcription Factors", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "Stanford University", 
          "id": "https://www.grid.ac/institutes/grid.168010.e", 
          "name": [
            "Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California 94305, USA", 
            "Department of Genetics, Stanford University, Stanford, California 94305, USA", 
            "Department of Pathology, Stanford University, Stanford, California 94305, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Lujan", 
        "givenName": "Ernesto", 
        "id": "sg:person.0656153011.17", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0656153011.17"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Stanford University", 
          "id": "https://www.grid.ac/institutes/grid.168010.e", 
          "name": [
            "Baxter Laboratory in Stem Cell Biology, Department of Microbiology and Immunology, Stanford University, Stanford, California 94305, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Zunder", 
        "givenName": "Eli R.", 
        "id": "sg:person.01337306653.25", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01337306653.25"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Stanford University", 
          "id": "https://www.grid.ac/institutes/grid.168010.e", 
          "name": [
            "Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California 94305, USA", 
            "Department of Pathology, Stanford University, Stanford, California 94305, USA", 
            "Department of Microbiology and Immunology, Stanford University, Stanford, California 94305, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Ng", 
        "givenName": "Yi Han", 
        "id": "sg:person.01275664762.54", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01275664762.54"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Stanford University", 
          "id": "https://www.grid.ac/institutes/grid.168010.e", 
          "name": [
            "Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California 94305, USA", 
            "Department of Pathology, Stanford University, Stanford, California 94305, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Goronzy", 
        "givenName": "Isabel N.", 
        "id": "sg:person.0671136261.34", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0671136261.34"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Stanford University", 
          "id": "https://www.grid.ac/institutes/grid.168010.e", 
          "name": [
            "Baxter Laboratory in Stem Cell Biology, Department of Microbiology and Immunology, Stanford University, Stanford, California 94305, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Nolan", 
        "givenName": "Garry P.", 
        "id": "sg:person.0772361007.36", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0772361007.36"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Stanford University", 
          "id": "https://www.grid.ac/institutes/grid.168010.e", 
          "name": [
            "Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California 94305, USA", 
            "Department of Pathology, Stanford University, Stanford, California 94305, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Wernig", 
        "givenName": "Marius", 
        "id": "sg:person.01256420377.73", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01256420377.73"
        ], 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "https://doi.org/10.1016/j.cell.2009.01.001", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1001400503"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.celrep.2013.05.015", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1003356117"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ncomms4678", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1003699666", 
          "https://doi.org/10.1038/ncomms4678"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nbt.1991", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1007715803", 
          "https://doi.org/10.1038/nbt.1991"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.stem.2008.02.001", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1008490443"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1073/pnas.1310291110", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1009370089"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.stem.2009.09.012", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1010339782"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ncomms6042", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1011820278", 
          "https://doi.org/10.1038/ncomms6042"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.cell.2012.11.039", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1014008509"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.stem.2012.11.008", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1014629697"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.stem.2015.01.015", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1014865399"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.stem.2015.01.015", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1014865399"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.cub.2009.08.025", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1018741034"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature08797", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1022463782", 
          "https://doi.org/10.1038/nature08797"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature08797", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1022463782", 
          "https://doi.org/10.1038/nature08797"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1159/000082134", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1024831530"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.stem.2010.04.014", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1027345170"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature08592", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1030291386", 
          "https://doi.org/10.1038/nature08592"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature08592", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1030291386", 
          "https://doi.org/10.1038/nature08592"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature12885", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1030759507", 
          "https://doi.org/10.1038/nature12885"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature12243", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1033219210", 
          "https://doi.org/10.1038/nature12243"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1021/ac901049w", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1033598272"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1021/ac901049w", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1033598272"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1126/science.1239278", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1035199503"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1093/bioinformatics/bts425", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1035518980"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature07056", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1037743725", 
          "https://doi.org/10.1038/nature07056"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.stem.2010.04.015", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1037783462"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature12587", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1040499216", 
          "https://doi.org/10.1038/nature12587"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/cyto.a.22067", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1040558357"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ng.2491", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1041935406", 
          "https://doi.org/10.1038/ng.2491"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/cyto.a.22271", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1046339096"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ng1117", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1048907095", 
          "https://doi.org/10.1038/ng1117"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ng1117", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1048907095", 
          "https://doi.org/10.1038/ng1117"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nbt1335", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1049953935", 
          "https://doi.org/10.1038/nbt1335"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.cell.2012.08.023", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1050505969"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.stem.2008.01.004", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1053248333"
        ], 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2015-04-01", 
    "datePublishedReg": "2015-04-01", 
    "description": "In the context of most induced pluripotent stem (iPS) cell reprogramming methods, heterogeneous populations of non-productive and staggered productive intermediates arise at different reprogramming time points. Despite recent reports claiming substantially increased reprogramming efficiencies using genetically modified donor cells, prospectively isolating distinct reprogramming intermediates remains an important goal to decipher reprogramming mechanisms. Previous attempts to identify surface markers of intermediate cell populations were based on the assumption that, during reprogramming, cells progressively lose donor cell identity and gradually acquire iPS cell properties. Here we report that iPS cell and epithelial markers, such as SSEA1 and EpCAM, respectively, are not predictive of reprogramming during early phases. Instead, in a systematic functional surface marker screen, we find that early reprogramming-prone cells express a unique set of surface markers, including CD73, CD49d and CD200, that are absent in both fibroblasts and iPS cells. Single-cell mass cytometry and prospective isolation show that these distinct intermediates are transient and bridge the gap between donor cell silencing and pluripotency marker acquisition during the early, presumably stochastic, reprogramming phase. Expression profiling reveals early upregulation of the transcriptional regulators Nr0b1 and Etv5 in this reprogramming state, preceding activation of key pluripotency regulators such as Rex1 (also known as Zfp42), Dppa2, Nanog and Sox2. Both factors are required for the generation of the early intermediate state and fully reprogrammed iPS cells, and thus represent some of the earliest known regulators of iPS cell induction. Our study deconvolutes the first steps in a hierarchical series of events that lead to pluripotency acquisition. ", 
    "genre": "research_article", 
    "id": "sg:pub.10.1038/nature14274", 
    "inLanguage": [
      "en"
    ], 
    "isAccessibleForFree": true, 
    "isFundedItemOf": [
      {
        "id": "sg:grant.6849108", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.2383101", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.6849086", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.2681824", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.2669689", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.7141965", 
        "type": "MonetaryGrant"
      }
    ], 
    "isPartOf": [
      {
        "id": "sg:journal.1018957", 
        "issn": [
          "0090-0028", 
          "1476-4687"
        ], 
        "name": "Nature", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "7552", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "521"
      }
    ], 
    "name": "Early reprogramming regulators identified by prospective isolation and mass cytometry", 
    "pagination": "352", 
    "productId": [
      {
        "name": "readcube_id", 
        "type": "PropertyValue", 
        "value": [
          "fa86a4a8bf2f7fea7e94b87b2124c726c2b2cf8196d614f9010ee2ad9f0074d5"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "25830878"
        ]
      }, 
      {
        "name": "nlm_unique_id", 
        "type": "PropertyValue", 
        "value": [
          "0410462"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1038/nature14274"
        ]
      }, 
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1052594762"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1038/nature14274", 
      "https://app.dimensions.ai/details/publication/pub.1052594762"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2019-04-10T22:19", 
    "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
    "sdPublisher": {
      "name": "Springer Nature - SN SciGraph project", 
      "type": "Organization"
    }, 
    "sdSource": "s3://com-uberresearch-data-dimensions-target-20181106-alternative/cleanup/v134/2549eaecd7973599484d7c17b260dba0a4ecb94b/merge/v9/a6c9fde33151104705d4d7ff012ea9563521a3ce/jats-lookup/v90/0000000001_0000000264/records_8690_00000426.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "https://www.nature.com/articles/nature14274"
  }
]
 

Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/nature14274'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/nature14274'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/nature14274'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/nature14274'


 

This table displays all metadata directly associated to this object as RDF triples.

325 TRIPLES      21 PREDICATES      84 URIs      45 LITERALS      34 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1038/nature14274 schema:about N0c8f7d2079db4d088e314d47261eae0d
2 N114f1671b84d43b09970ffb630e2c051
3 N1a90e4906da949c6bc207011cad44d8f
4 N2dfe9a559b3549c790bdc001e1a9bed3
5 N37b22ba05b5047f2903162a147f00e5e
6 N3b08647173b04e6baf7f53395149149f
7 N451bb683bcf94fc28fb6523fe82b579d
8 N49273f12b9874143be9a24d34c7a1c14
9 N4c9c3e69ce88489db5799847eaee5e19
10 N65710f0bda22413498c632c091ca3aa9
11 N723ecfce9420467f8d1756502f5f580c
12 N76d2622f41e94dd1b3968ac01111748f
13 N7a86d833ef8d4dc2a33f1e267f61acd1
14 N7a8797cf99234d64ab65522eaa326847
15 N8272ebe0769d4ef299f0309736ede6ba
16 N94e1df9faee04209b8ac3eaa55f9a270
17 N9ea6502092bd4481b65e30d328a9ce01
18 Naaf38e7926574c0b95365bee75e50eb9
19 Nb7206222e39d4ee4a5c983297ed7ff57
20 Ncd84fab8781847d7af507f236b15a62b
21 Nda6752aababf4550a535c98f9cd72bc6
22 Ndf486153303346dd8e486210fb337530
23 Ne6d3fc58867e438f80265013941c29dd
24 Ne8d4e32fa7f7453f8aa4c75d048dbfe5
25 Nface9745a5a94790834d3f3d5acf0926
26 anzsrc-for:06
27 anzsrc-for:0601
28 schema:author N4c7c770a5e89476fa12042fc336f1279
29 schema:citation sg:pub.10.1038/nature07056
30 sg:pub.10.1038/nature08592
31 sg:pub.10.1038/nature08797
32 sg:pub.10.1038/nature12243
33 sg:pub.10.1038/nature12587
34 sg:pub.10.1038/nature12885
35 sg:pub.10.1038/nbt.1991
36 sg:pub.10.1038/nbt1335
37 sg:pub.10.1038/ncomms4678
38 sg:pub.10.1038/ncomms6042
39 sg:pub.10.1038/ng.2491
40 sg:pub.10.1038/ng1117
41 https://doi.org/10.1002/cyto.a.22067
42 https://doi.org/10.1002/cyto.a.22271
43 https://doi.org/10.1016/j.cell.2009.01.001
44 https://doi.org/10.1016/j.cell.2012.08.023
45 https://doi.org/10.1016/j.cell.2012.11.039
46 https://doi.org/10.1016/j.celrep.2013.05.015
47 https://doi.org/10.1016/j.cub.2009.08.025
48 https://doi.org/10.1016/j.stem.2008.01.004
49 https://doi.org/10.1016/j.stem.2008.02.001
50 https://doi.org/10.1016/j.stem.2009.09.012
51 https://doi.org/10.1016/j.stem.2010.04.014
52 https://doi.org/10.1016/j.stem.2010.04.015
53 https://doi.org/10.1016/j.stem.2012.11.008
54 https://doi.org/10.1016/j.stem.2015.01.015
55 https://doi.org/10.1021/ac901049w
56 https://doi.org/10.1073/pnas.1310291110
57 https://doi.org/10.1093/bioinformatics/bts425
58 https://doi.org/10.1126/science.1239278
59 https://doi.org/10.1159/000082134
60 schema:datePublished 2015-04-01
61 schema:datePublishedReg 2015-04-01
62 schema:description In the context of most induced pluripotent stem (iPS) cell reprogramming methods, heterogeneous populations of non-productive and staggered productive intermediates arise at different reprogramming time points. Despite recent reports claiming substantially increased reprogramming efficiencies using genetically modified donor cells, prospectively isolating distinct reprogramming intermediates remains an important goal to decipher reprogramming mechanisms. Previous attempts to identify surface markers of intermediate cell populations were based on the assumption that, during reprogramming, cells progressively lose donor cell identity and gradually acquire iPS cell properties. Here we report that iPS cell and epithelial markers, such as SSEA1 and EpCAM, respectively, are not predictive of reprogramming during early phases. Instead, in a systematic functional surface marker screen, we find that early reprogramming-prone cells express a unique set of surface markers, including CD73, CD49d and CD200, that are absent in both fibroblasts and iPS cells. Single-cell mass cytometry and prospective isolation show that these distinct intermediates are transient and bridge the gap between donor cell silencing and pluripotency marker acquisition during the early, presumably stochastic, reprogramming phase. Expression profiling reveals early upregulation of the transcriptional regulators Nr0b1 and Etv5 in this reprogramming state, preceding activation of key pluripotency regulators such as Rex1 (also known as Zfp42), Dppa2, Nanog and Sox2. Both factors are required for the generation of the early intermediate state and fully reprogrammed iPS cells, and thus represent some of the earliest known regulators of iPS cell induction. Our study deconvolutes the first steps in a hierarchical series of events that lead to pluripotency acquisition.
63 schema:genre research_article
64 schema:inLanguage en
65 schema:isAccessibleForFree true
66 schema:isPartOf N35db6c4a365744829740ccb4003b4c6d
67 N3c26ea60912047089eef98bc09f910dd
68 sg:journal.1018957
69 schema:name Early reprogramming regulators identified by prospective isolation and mass cytometry
70 schema:pagination 352
71 schema:productId N7ef57fb294dd45ffbf77e81adb1c56b1
72 N9ce26121132543729e05e8dd1d26a15f
73 Na71740b7b2794944a1f36b44072e3bea
74 Nbec7ad02f727460988ba9dc00760e6e3
75 Nff01193356bc4ebeb112bb6cb93713e3
76 schema:sameAs https://app.dimensions.ai/details/publication/pub.1052594762
77 https://doi.org/10.1038/nature14274
78 schema:sdDatePublished 2019-04-10T22:19
79 schema:sdLicense https://scigraph.springernature.com/explorer/license/
80 schema:sdPublisher N0d9eb14e05804d00b43c66fa824771b5
81 schema:url https://www.nature.com/articles/nature14274
82 sgo:license sg:explorer/license/
83 sgo:sdDataset articles
84 rdf:type schema:ScholarlyArticle
85 N0c8f7d2079db4d088e314d47261eae0d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
86 schema:name Integrin alpha4
87 rdf:type schema:DefinedTerm
88 N0d9eb14e05804d00b43c66fa824771b5 schema:name Springer Nature - SN SciGraph project
89 rdf:type schema:Organization
90 N114f1671b84d43b09970ffb630e2c051 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
91 schema:name Gene Expression Profiling
92 rdf:type schema:DefinedTerm
93 N1a90e4906da949c6bc207011cad44d8f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
94 schema:name Epithelial Cells
95 rdf:type schema:DefinedTerm
96 N21cd44dd36e641c38a288fcc8afba34a rdf:first sg:person.0671136261.34
97 rdf:rest Nb37968779fb347979f0b29a38638bd04
98 N2dfe9a559b3549c790bdc001e1a9bed3 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
99 schema:name Mice
100 rdf:type schema:DefinedTerm
101 N35db6c4a365744829740ccb4003b4c6d schema:issueNumber 7552
102 rdf:type schema:PublicationIssue
103 N37b22ba05b5047f2903162a147f00e5e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
104 schema:name Induced Pluripotent Stem Cells
105 rdf:type schema:DefinedTerm
106 N3b08647173b04e6baf7f53395149149f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
107 schema:name Cell Adhesion Molecules
108 rdf:type schema:DefinedTerm
109 N3c26ea60912047089eef98bc09f910dd schema:volumeNumber 521
110 rdf:type schema:PublicationVolume
111 N451bb683bcf94fc28fb6523fe82b579d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
112 schema:name Transcription Factors
113 rdf:type schema:DefinedTerm
114 N49273f12b9874143be9a24d34c7a1c14 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
115 schema:name Antigens, Neoplasm
116 rdf:type schema:DefinedTerm
117 N4c7c770a5e89476fa12042fc336f1279 rdf:first sg:person.0656153011.17
118 rdf:rest Nc2959c74d2764129a01e3419557c9368
119 N4c9c3e69ce88489db5799847eaee5e19 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
120 schema:name Lewis X Antigen
121 rdf:type schema:DefinedTerm
122 N4e596a691a654b29bbe9a27c25a199de rdf:first sg:person.01275664762.54
123 rdf:rest N21cd44dd36e641c38a288fcc8afba34a
124 N65710f0bda22413498c632c091ca3aa9 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
125 schema:name Biomarkers
126 rdf:type schema:DefinedTerm
127 N723ecfce9420467f8d1756502f5f580c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
128 schema:name SOXB1 Transcription Factors
129 rdf:type schema:DefinedTerm
130 N76d2622f41e94dd1b3968ac01111748f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
131 schema:name Antigens, CD
132 rdf:type schema:DefinedTerm
133 N7a86d833ef8d4dc2a33f1e267f61acd1 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
134 schema:name Animals
135 rdf:type schema:DefinedTerm
136 N7a8797cf99234d64ab65522eaa326847 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
137 schema:name Flow Cytometry
138 rdf:type schema:DefinedTerm
139 N7ef57fb294dd45ffbf77e81adb1c56b1 schema:name pubmed_id
140 schema:value 25830878
141 rdf:type schema:PropertyValue
142 N8272ebe0769d4ef299f0309736ede6ba schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
143 schema:name Epithelial Cell Adhesion Molecule
144 rdf:type schema:DefinedTerm
145 N94e1df9faee04209b8ac3eaa55f9a270 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
146 schema:name Time Factors
147 rdf:type schema:DefinedTerm
148 N9ce26121132543729e05e8dd1d26a15f schema:name dimensions_id
149 schema:value pub.1052594762
150 rdf:type schema:PropertyValue
151 N9ea6502092bd4481b65e30d328a9ce01 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
152 schema:name Nanog Homeobox Protein
153 rdf:type schema:DefinedTerm
154 Na71740b7b2794944a1f36b44072e3bea schema:name nlm_unique_id
155 schema:value 0410462
156 rdf:type schema:PropertyValue
157 Na7991d002f144fb1abcc64c8fad51f56 rdf:first sg:person.01256420377.73
158 rdf:rest rdf:nil
159 Naaf38e7926574c0b95365bee75e50eb9 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
160 schema:name 5'-Nucleotidase
161 rdf:type schema:DefinedTerm
162 Nb37968779fb347979f0b29a38638bd04 rdf:first sg:person.0772361007.36
163 rdf:rest Na7991d002f144fb1abcc64c8fad51f56
164 Nb7206222e39d4ee4a5c983297ed7ff57 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
165 schema:name Nuclear Proteins
166 rdf:type schema:DefinedTerm
167 Nbec7ad02f727460988ba9dc00760e6e3 schema:name readcube_id
168 schema:value fa86a4a8bf2f7fea7e94b87b2124c726c2b2cf8196d614f9010ee2ad9f0074d5
169 rdf:type schema:PropertyValue
170 Nc2959c74d2764129a01e3419557c9368 rdf:first sg:person.01337306653.25
171 rdf:rest N4e596a691a654b29bbe9a27c25a199de
172 Ncd84fab8781847d7af507f236b15a62b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
173 schema:name Fibroblasts
174 rdf:type schema:DefinedTerm
175 Nda6752aababf4550a535c98f9cd72bc6 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
176 schema:name Cellular Reprogramming
177 rdf:type schema:DefinedTerm
178 Ndf486153303346dd8e486210fb337530 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
179 schema:name DAX-1 Orphan Nuclear Receptor
180 rdf:type schema:DefinedTerm
181 Ne6d3fc58867e438f80265013941c29dd schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
182 schema:name Homeodomain Proteins
183 rdf:type schema:DefinedTerm
184 Ne8d4e32fa7f7453f8aa4c75d048dbfe5 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
185 schema:name Cell Separation
186 rdf:type schema:DefinedTerm
187 Nface9745a5a94790834d3f3d5acf0926 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
188 schema:name DNA-Binding Proteins
189 rdf:type schema:DefinedTerm
190 Nff01193356bc4ebeb112bb6cb93713e3 schema:name doi
191 schema:value 10.1038/nature14274
192 rdf:type schema:PropertyValue
193 anzsrc-for:06 schema:inDefinedTermSet anzsrc-for:
194 schema:name Biological Sciences
195 rdf:type schema:DefinedTerm
196 anzsrc-for:0601 schema:inDefinedTermSet anzsrc-for:
197 schema:name Biochemistry and Cell Biology
198 rdf:type schema:DefinedTerm
199 sg:grant.2383101 http://pending.schema.org/fundedItem sg:pub.10.1038/nature14274
200 rdf:type schema:MonetaryGrant
201 sg:grant.2669689 http://pending.schema.org/fundedItem sg:pub.10.1038/nature14274
202 rdf:type schema:MonetaryGrant
203 sg:grant.2681824 http://pending.schema.org/fundedItem sg:pub.10.1038/nature14274
204 rdf:type schema:MonetaryGrant
205 sg:grant.6849086 http://pending.schema.org/fundedItem sg:pub.10.1038/nature14274
206 rdf:type schema:MonetaryGrant
207 sg:grant.6849108 http://pending.schema.org/fundedItem sg:pub.10.1038/nature14274
208 rdf:type schema:MonetaryGrant
209 sg:grant.7141965 http://pending.schema.org/fundedItem sg:pub.10.1038/nature14274
210 rdf:type schema:MonetaryGrant
211 sg:journal.1018957 schema:issn 0090-0028
212 1476-4687
213 schema:name Nature
214 rdf:type schema:Periodical
215 sg:person.01256420377.73 schema:affiliation https://www.grid.ac/institutes/grid.168010.e
216 schema:familyName Wernig
217 schema:givenName Marius
218 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01256420377.73
219 rdf:type schema:Person
220 sg:person.01275664762.54 schema:affiliation https://www.grid.ac/institutes/grid.168010.e
221 schema:familyName Ng
222 schema:givenName Yi Han
223 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01275664762.54
224 rdf:type schema:Person
225 sg:person.01337306653.25 schema:affiliation https://www.grid.ac/institutes/grid.168010.e
226 schema:familyName Zunder
227 schema:givenName Eli R.
228 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01337306653.25
229 rdf:type schema:Person
230 sg:person.0656153011.17 schema:affiliation https://www.grid.ac/institutes/grid.168010.e
231 schema:familyName Lujan
232 schema:givenName Ernesto
233 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0656153011.17
234 rdf:type schema:Person
235 sg:person.0671136261.34 schema:affiliation https://www.grid.ac/institutes/grid.168010.e
236 schema:familyName Goronzy
237 schema:givenName Isabel N.
238 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0671136261.34
239 rdf:type schema:Person
240 sg:person.0772361007.36 schema:affiliation https://www.grid.ac/institutes/grid.168010.e
241 schema:familyName Nolan
242 schema:givenName Garry P.
243 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0772361007.36
244 rdf:type schema:Person
245 sg:pub.10.1038/nature07056 schema:sameAs https://app.dimensions.ai/details/publication/pub.1037743725
246 https://doi.org/10.1038/nature07056
247 rdf:type schema:CreativeWork
248 sg:pub.10.1038/nature08592 schema:sameAs https://app.dimensions.ai/details/publication/pub.1030291386
249 https://doi.org/10.1038/nature08592
250 rdf:type schema:CreativeWork
251 sg:pub.10.1038/nature08797 schema:sameAs https://app.dimensions.ai/details/publication/pub.1022463782
252 https://doi.org/10.1038/nature08797
253 rdf:type schema:CreativeWork
254 sg:pub.10.1038/nature12243 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033219210
255 https://doi.org/10.1038/nature12243
256 rdf:type schema:CreativeWork
257 sg:pub.10.1038/nature12587 schema:sameAs https://app.dimensions.ai/details/publication/pub.1040499216
258 https://doi.org/10.1038/nature12587
259 rdf:type schema:CreativeWork
260 sg:pub.10.1038/nature12885 schema:sameAs https://app.dimensions.ai/details/publication/pub.1030759507
261 https://doi.org/10.1038/nature12885
262 rdf:type schema:CreativeWork
263 sg:pub.10.1038/nbt.1991 schema:sameAs https://app.dimensions.ai/details/publication/pub.1007715803
264 https://doi.org/10.1038/nbt.1991
265 rdf:type schema:CreativeWork
266 sg:pub.10.1038/nbt1335 schema:sameAs https://app.dimensions.ai/details/publication/pub.1049953935
267 https://doi.org/10.1038/nbt1335
268 rdf:type schema:CreativeWork
269 sg:pub.10.1038/ncomms4678 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003699666
270 https://doi.org/10.1038/ncomms4678
271 rdf:type schema:CreativeWork
272 sg:pub.10.1038/ncomms6042 schema:sameAs https://app.dimensions.ai/details/publication/pub.1011820278
273 https://doi.org/10.1038/ncomms6042
274 rdf:type schema:CreativeWork
275 sg:pub.10.1038/ng.2491 schema:sameAs https://app.dimensions.ai/details/publication/pub.1041935406
276 https://doi.org/10.1038/ng.2491
277 rdf:type schema:CreativeWork
278 sg:pub.10.1038/ng1117 schema:sameAs https://app.dimensions.ai/details/publication/pub.1048907095
279 https://doi.org/10.1038/ng1117
280 rdf:type schema:CreativeWork
281 https://doi.org/10.1002/cyto.a.22067 schema:sameAs https://app.dimensions.ai/details/publication/pub.1040558357
282 rdf:type schema:CreativeWork
283 https://doi.org/10.1002/cyto.a.22271 schema:sameAs https://app.dimensions.ai/details/publication/pub.1046339096
284 rdf:type schema:CreativeWork
285 https://doi.org/10.1016/j.cell.2009.01.001 schema:sameAs https://app.dimensions.ai/details/publication/pub.1001400503
286 rdf:type schema:CreativeWork
287 https://doi.org/10.1016/j.cell.2012.08.023 schema:sameAs https://app.dimensions.ai/details/publication/pub.1050505969
288 rdf:type schema:CreativeWork
289 https://doi.org/10.1016/j.cell.2012.11.039 schema:sameAs https://app.dimensions.ai/details/publication/pub.1014008509
290 rdf:type schema:CreativeWork
291 https://doi.org/10.1016/j.celrep.2013.05.015 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003356117
292 rdf:type schema:CreativeWork
293 https://doi.org/10.1016/j.cub.2009.08.025 schema:sameAs https://app.dimensions.ai/details/publication/pub.1018741034
294 rdf:type schema:CreativeWork
295 https://doi.org/10.1016/j.stem.2008.01.004 schema:sameAs https://app.dimensions.ai/details/publication/pub.1053248333
296 rdf:type schema:CreativeWork
297 https://doi.org/10.1016/j.stem.2008.02.001 schema:sameAs https://app.dimensions.ai/details/publication/pub.1008490443
298 rdf:type schema:CreativeWork
299 https://doi.org/10.1016/j.stem.2009.09.012 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010339782
300 rdf:type schema:CreativeWork
301 https://doi.org/10.1016/j.stem.2010.04.014 schema:sameAs https://app.dimensions.ai/details/publication/pub.1027345170
302 rdf:type schema:CreativeWork
303 https://doi.org/10.1016/j.stem.2010.04.015 schema:sameAs https://app.dimensions.ai/details/publication/pub.1037783462
304 rdf:type schema:CreativeWork
305 https://doi.org/10.1016/j.stem.2012.11.008 schema:sameAs https://app.dimensions.ai/details/publication/pub.1014629697
306 rdf:type schema:CreativeWork
307 https://doi.org/10.1016/j.stem.2015.01.015 schema:sameAs https://app.dimensions.ai/details/publication/pub.1014865399
308 rdf:type schema:CreativeWork
309 https://doi.org/10.1021/ac901049w schema:sameAs https://app.dimensions.ai/details/publication/pub.1033598272
310 rdf:type schema:CreativeWork
311 https://doi.org/10.1073/pnas.1310291110 schema:sameAs https://app.dimensions.ai/details/publication/pub.1009370089
312 rdf:type schema:CreativeWork
313 https://doi.org/10.1093/bioinformatics/bts425 schema:sameAs https://app.dimensions.ai/details/publication/pub.1035518980
314 rdf:type schema:CreativeWork
315 https://doi.org/10.1126/science.1239278 schema:sameAs https://app.dimensions.ai/details/publication/pub.1035199503
316 rdf:type schema:CreativeWork
317 https://doi.org/10.1159/000082134 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024831530
318 rdf:type schema:CreativeWork
319 https://www.grid.ac/institutes/grid.168010.e schema:alternateName Stanford University
320 schema:name Baxter Laboratory in Stem Cell Biology, Department of Microbiology and Immunology, Stanford University, Stanford, California 94305, USA
321 Department of Genetics, Stanford University, Stanford, California 94305, USA
322 Department of Microbiology and Immunology, Stanford University, Stanford, California 94305, USA
323 Department of Pathology, Stanford University, Stanford, California 94305, USA
324 Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California 94305, USA
325 rdf:type schema:Organization
 




Preview window. Press ESC to close (or click here)


...