Journal article Open Access

Tumor to normal single-cell mRNA comparisons reveal a pan-neuroblastoma cancer cell

Kildisiute, G.; Kholosy, W.; Young, M.; Roberts, K.; Elmentaite, R.; R. van Hooff, S.; Pacyna, C.; Khabirova, E.; Piapi, A.; Thevanesan, C.; Bugallo-Blanco, E.; Burke, C.; Mamanova, L.; M. Keller, K.; Langenberg-Ververgaert, K.; Lijnzaad, P.; Margaritis, T.; Holstege, F.; L. Tas, M.; H.W.A. Wijnen, M.; M. van Noesel, M.; del Valle, I.; Barone, G.; van der Linden, R.; Duncan, C.; Anderson, J.; Achermann, J.; Haniffa, M.; Teichmann, S.; Rampling, D.; Sebire, N.; He, X.; R. de Krijger, R.; Barker, R.; Meyer, K.; Bayraktar, O.; Straathof, K.; Molenaar, J.; Behjati, S.


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      <creatorName>Pacyna, C.</creatorName>
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      <creatorName>Khabirova, E.</creatorName>
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      <creatorName>Piapi, A.</creatorName>
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      <creatorName>Thevanesan, C.</creatorName>
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      <familyName>Thevanesan</familyName>
      <affiliation>UCL Great Ormond Street Institute of Child Health</affiliation>
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      <creatorName>Bugallo-Blanco, E.</creatorName>
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      <creatorName>Mamanova, L.</creatorName>
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      <creatorName>M. Keller, K.</creatorName>
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      <creatorName>Langenberg-Ververgaert, K.</creatorName>
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      <creatorName>Lijnzaad, P.</creatorName>
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      <creatorName>Margaritis, T.</creatorName>
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      <familyName>Margaritis</familyName>
      <affiliation>Princess Máxima Center for Pediatric Oncology</affiliation>
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      <creatorName>Holstege, F.</creatorName>
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      <familyName>Holstege</familyName>
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      <creatorName>L. Tas, M.</creatorName>
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      <familyName>L. Tas</familyName>
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      <creatorName>H.W.A. Wijnen, M.</creatorName>
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      <creatorName>del Valle, I.</creatorName>
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      <creatorName>Barone, G.</creatorName>
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      <familyName>Barone</familyName>
      <affiliation>Great Ormond Street Hospital for Children (GOSH)</affiliation>
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      <creatorName>van der Linden, R.</creatorName>
      <givenName>R.</givenName>
      <familyName>van der Linden</familyName>
      <affiliation>Hubrecht Institute</affiliation>
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      <creatorName>Duncan, C.</creatorName>
      <givenName>C.</givenName>
      <familyName>Duncan</familyName>
      <affiliation>Hubrecht Institute</affiliation>
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      <creatorName>Anderson, J.</creatorName>
      <givenName>J.</givenName>
      <familyName>Anderson</familyName>
      <affiliation>Hubrecht Institute</affiliation>
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      <creatorName>Achermann, J.</creatorName>
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      <familyName>Achermann</familyName>
      <affiliation>UCL Great Ormond Street Institute of Child Health</affiliation>
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      <creatorName>Haniffa, M.</creatorName>
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      <familyName>Haniffa</familyName>
      <affiliation>Institute of Cellular Medicine, Newcastle University</affiliation>
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      <creatorName>Teichmann, S.</creatorName>
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      <familyName>Teichmann</familyName>
      <affiliation>Wellcome Sanger Institute, CB10 1SA Hinxton, UK</affiliation>
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      <creatorName>Rampling, D.</creatorName>
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      <creatorName>Sebire, N.</creatorName>
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      <affiliation>Great Ormond Street Hospital for Children (GOSH)</affiliation>
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      <creatorName>He, X.</creatorName>
      <givenName>X.</givenName>
      <familyName>He</familyName>
      <affiliation>MRC-WT Cambridge Stem Cell Institute, University of Cambridge</affiliation>
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      <creatorName>R. de Krijger, R.</creatorName>
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      <familyName>R. de Krijger</familyName>
      <affiliation>Department of Pathology, University Medical Center Utrecht</affiliation>
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      <creatorName>Barker, R.</creatorName>
      <givenName>R.</givenName>
      <familyName>Barker</familyName>
      <affiliation>MRC-WT Cambridge Stem Cell Institute, University of Cambridge</affiliation>
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      <creatorName>Meyer, K.</creatorName>
      <givenName>K.</givenName>
      <familyName>Meyer</familyName>
      <affiliation>Wellcome Sanger Institute, CB10 1SA Hinxton, UK</affiliation>
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      <creatorName>Bayraktar, O.</creatorName>
      <givenName>O.</givenName>
      <familyName>Bayraktar</familyName>
      <affiliation>Wellcome Sanger Institute, CB10 1SA Hinxton, UK</affiliation>
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      <creatorName>Straathof, K.</creatorName>
      <givenName>K.</givenName>
      <familyName>Straathof</familyName>
      <affiliation>UCL Great Ormond Street Institute of Child Health</affiliation>
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      <creatorName>Molenaar, J.</creatorName>
      <givenName>J.</givenName>
      <familyName>Molenaar</familyName>
      <affiliation>Princess Máxima Center for Pediatric Oncology</affiliation>
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    <creator>
      <creatorName>Behjati, S.</creatorName>
      <givenName>S.</givenName>
      <familyName>Behjati</familyName>
      <affiliation>Department of Paediatrics, University of Cambridge</affiliation>
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  </creators>
  <titles>
    <title>Tumor to normal single-cell mRNA comparisons reveal a pan-neuroblastoma cancer cell</title>
  </titles>
  <publisher>Zenodo</publisher>
  <publicationYear>2021</publicationYear>
  <dates>
    <date dateType="Issued">2021-02-05</date>
  </dates>
  <language>en</language>
  <resourceType resourceTypeGeneral="JournalArticle"/>
  <alternateIdentifiers>
    <alternateIdentifier alternateIdentifierType="url">https://zenodo.org/record/4636481</alternateIdentifier>
  </alternateIdentifiers>
  <relatedIdentifiers>
    <relatedIdentifier relatedIdentifierType="DOI" relationType="IsIdenticalTo">10.1126/sciadv.abd3311</relatedIdentifier>
    <relatedIdentifier relatedIdentifierType="URL" relationType="IsPartOf">https://zenodo.org/communities/ipc</relatedIdentifier>
  </relatedIdentifiers>
  <rightsList>
    <rights rightsURI="https://creativecommons.org/licenses/by/4.0/legalcode">Creative Commons Attribution 4.0 International</rights>
    <rights rightsURI="info:eu-repo/semantics/openAccess">Open Access</rights>
  </rightsList>
  <descriptions>
    <description descriptionType="Abstract">&lt;p&gt;Neuroblastoma is a childhood cancer that resembles the developmental stages of the neural crest. It is not established what developmental processes neuroblastoma cancer cells represent. Here, we sought to reveal the phenotype of neuroblastoma cancer cells by comparing cancer (&lt;em&gt;n&lt;/em&gt;&amp;nbsp;= 19,723) with normal fetal adrenal single-cell transcriptomes (&lt;em&gt;n&lt;/em&gt;&amp;nbsp;= 57,972). Our principal finding was that the neuroblastoma cancer cell resembled fetal sympathoblasts, but no other fetal adrenal cell type. The sympathoblastic state was a universal feature of neuroblastoma cells, transcending cell cluster diversity, individual patients, and clinical phenotypes. We substantiated our findings in 650 neuroblastoma bulk transcriptomes and by integrating canonical features of the neuroblastoma genome with transcriptional signals. Overall, our observations indicate that a pan-neuroblastoma cancer cell state exists, which may be attractive for novel immunotherapeutic and targeted avenues.&lt;/p&gt;</description>
  </descriptions>
  <fundingReferences>
    <fundingReference>
      <funderName>European Commission</funderName>
      <funderIdentifier funderIdentifierType="Crossref Funder ID">10.13039/100010661</funderIdentifier>
      <awardNumber awardURI="info:eu-repo/grantAgreement/EC/H2020/826121/">826121</awardNumber>
      <awardTitle>individualizedPaediatricCure: Cloud-based virtual-patient models for precision paediatric oncology</awardTitle>
    </fundingReference>
  </fundingReferences>
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